C2 136 Disclaimer — This paper partially fulfills a writing requirement for first year (freshman) engineering students at the University of Pittsburgh Swanson School of Engineering. This paper is a student, not a professional, paper. This paper is based on publicly available information and may not be provided complete analyses of all relevant data. If this paper is used for any purpose other than these authors’ partial fulfillment of a writing requirement for first year (freshman) engineering students at the University of Pittsburgh Swanson School of Engineering, the user does so at his or her own risk. MICRORNAS: THE FUTURE OF CANCER TREATMENT Megha Murthy, [email protected], Mahboobin 10:00, Shivani Tuli, [email protected], Budny 10:00 Abstract — Breast cancer affects millions of women each year and researchers and scientists are still looking for a way to detect it. Currently, various types of medical imaging techniques, such as magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning, are used to detect tumors in the body. However, these imaging modalities cannot detect tumors until they are too large and malignant to cure. To improve clinical outcomes, it would be beneficial to find a method for early detection of cancer at the cellular level and target the disease before it develops further. Efficiency and cost-effectiveness in detection and treatment can be improved by conducting experiments and research at the cellular level, for example on blood samples. MicroRNAs, fragments of gene carriers that inhibit the translation of RNA to protein, can help medical professionals detect breast cancer, enabling doctors to often prevent further cancer growth. Extracting blood and screening it for high microRNA levels is a good indicator of existing cancer. By detecting cancer before it develops into malignant tumors, doctors will have more time to determine a treatment that works best for the patient. This technology would enable bioengineers and researchers to find a better treatment for cancer. The important factor to consider when dealing with cancer treatment and detection is sustainability of the technology. Sustainability involves providing health benefits and improving the quality of life of the environment. Using microRNAs will benefit both life and public health. Combining microRNA technology with other treatment methods, such as drug therapy, will make cancer therapy more accessible. Detecting cancer early will also give more hope to patients who may think there is no hope for a cure. It will give medical professionals more time to find the most appropriate treatment for everyone. MicroRNAs are the future to detecting and treating cancer. Every day, thousands of hospitals flood with patients who seek treatment for breast cancer, the most common type of cancer in women. Doctors, scientists, and engineers continue to scramble to find an efficient, inexpensive treatment for breast cancer. Understanding what breast cancer is and how it spreads throughout the body will enable researchers to find a better treatment than conventional approaches. Breast Cancer Pathogenesis Cancer is a genetic disease caused by alterations of gene expressions. Gene alterations occur during DNA replication. In some cases, there will be a mistake during DNA replication where one base is incorrectly paired up with another base (an adenine (A) is paired with a cytosine (C)). Although there are enzymes whose job is to fix these errors, the incorrect pairs are sometimes incorporated into the DNA strand. Once this occurs, the mistake is continued during DNA transcription and mRNA translation. These mutations may give rise to cancerous cells, which will then continue to spread throughout the body as shown in the figure below. Key Words—Breast Cancer, Cancer Detection, Cancer Research, Gene Therapy, Genetic Engineering, microRNA, Tumor Suppressors HISTORY OF BREAST CANCER TREATMENT AND MICRORNAS University of Pittsburgh Swanson School of Engineering 1 3.31.2017 FIGURE 1 [1] Cancer Arising from Mutated DNA Megha Murthy Shivani Tuli Parts of the DNA strand are affected in a cancerous cell. When paired with the wrong base, there is a higher chance that mutations within the genes will arise. This means that there is a greater chance an individual will have cancerous cells running through their body. Breast cancer, like other cancers, occurs when the cells bypass the cellular checkpoints during normal cell division. Unlike healthy cells, cancer cells ignore cues for apoptosis, programmed cell death, and modify their molecular pathways such that they keep dividing, eventually losing control, and sometimes metastasizing to the rest of the body [2]. Predictions about where the cancer spreads will enable doctors to find a treatment before the cancer cells have time to transform from benign tumors to malignant tumors. Cancerous cells can spread through the body in two ways: through the blood vessels or the lymph system. Scientists recently discovered that cancer cells enter blood vessels at a specific site, the tumor microenvironment of metastasis (TMEM), where endothelial cells (cells that line blood vessels), perivascular macrophages (immune cells), and tumor cells that produce the protein mena (increases ability of cell to invade other cells) come into direct contact with one another. When the three cells come into contact, they release a protein which increases the permeability of the blood vessels, allowing the cancerous cells to enter the bloodstream [3]. However, it is most common for cancer to spread through the lymph system because this system runs through the whole body, as shown below. The lymph system employs various mechanisms to prevent malicious cells from entering the system. However, when cancer cells enter the system, the lymph nodes, which filter out infectious substances, start to swell up. At this stage, under a high-powered microscope, the type of cancer cell, such as breast cancer, becomes identifiable [4]. FIGURE 2 [4] The lymph system. Once cancer enters the lymph system, it can essentially travel to any part of the body. MicroRNAs Improve Upon Past Treatment Methods In recent years, the methods for detecting and treating cancer have vastly improved. In the past and still today, doctors use medical imaging to detect cancer. Physicians use x-ray imaging to check for the presence of breast cancer in dense tissues as these tissues are more likely to contain cancerous cells. However, x-ray images only visualize a certain area of the breast and therefore, fail to accurately depict the entire scope of the breast. Sonographies reflect sound waves off the breast tissues and display an image of the breast. This allows doctors to check for the presence of cancer based on the developed image [5]. Like the x-ray, sonographies also require a lot of time to process the image and may not accurately depict all features of the breast where cancer is present. Currently, researchers at various universities are investigating a simple, inexpensive blood test that can detect cancer in the body by checking for the presence of microRNAs. According to these researchers, microRNAs control some of the major life processes by preventing genetic code from executing. Since cancer cells are descendants of healthy cells, which contain microRNAs, having too little or too much of a particular microRNA can signify tumor growth [6]. Researchers at the University of Michigan have created a new method for detecting any sort of RNA from the blood. Initially, researchers believed RNA only acted as a messenger and carried out DNA’s genetic code to the proteins. However, after sequencing the human genome, they discovered that most RNAs do not act as messengers [6]. Scientists at this university hypothesize that when cancer cells die, they release microRNAs and communicate with the microRNAs to send them into the bloodstream as hormones. In one experiment, researchers at the University of Michigan coated a glass slide with “capture probes” and dropped samples of solutions containing different types of microRNAs onto the coated slides to detect microRNAs in the bloodstream. To test whether the probes caught any microRNAs, the researchers placed engineered fluorescent DNA strands that bind to the microRNA and emit light when bound to the microRNA onto the slides. This method is efficient, reliable, and more direct than other cancer methods [6]. Compared to medical imaging, extracting microRNA from the blood offers a safe, inexpensive method of detecting cancer in the blood. Certain types of medical imaging often involve radiation, which can have negative side effects on the body if absorbed in large doses, such as those used for cancer treatment. 2 Megha Murthy Shivani Tuli Similarly, miR-10 aids in the growth of breast cancer. An overexpression of this type of microRNA can lead to a cancer cell invasion as well as the spread of breast cancer. Like miR10, an overexpression in miR-21 signifies an increase in the spread and growth of breast cancer cells [8]. Figure 3, below, classifies the properties of several types of microRNAs as either tumor suppressors or oncogenes. MOLECULAR FUNCTION OF MICRORNAS Cancer is a progressive disease and advances through the body in many stages beginning with stage 1, which is considered the benign stage, to stage 5, the most malignant stage. During the benign stage, the tumor has yet to spread to the rest of the body and is situated in one area where it can be monitored. However, if not treated, the tumor can transform undergoing a phenotypic change and spreading rapidly to the rest of the body. Unlike other cells, cancerous cells can bypass regulation by external growth signals, evade programmed cell death, overcome replication limits, and form new tumors through cell division [7]. There are two major categories of genes linked with cancer: oncogenes and tumor suppressors, both of which are protein coding genes. Oncogenes consist of growth factors, apoptosis regulators, and signal transducers. Overexpression of oncogenes, when activated by genetic alterations that amplify the genes, can drive tumor development. Tumor suppressors, on the other hand, dysregulate a tumor’s functions to keep it from spreading and harming the body. Essentially, oncogenes influence tumor growth while tumor suppressors, as suggested by their name, suppress the tumor and control the growth [7]. Recently, scientists have included microRNAs in their definition of oncogenes and tumor suppressors. Classified as a group of non-coding genes, microRNAs control gene regulation and expression as well as regulate several metabolic and cellular pathways, especially controlling cell proliferation, differentiation, and survival [7]. MicroRNAs regulate gene expression and depend on the internal and environmental conditions at any given time. Since cancer is a genetic disease that is affected by the alteration of a gene expressed in the body, microRNAs in the body can manipulate which genes are expressed in the body. Until recently, scientists had no real concept of a microRNA’s function in the body and what role the microRNAs played in breast physiology. In an article about the various functions of microRNAs, researchers conducted an examination on different types of microRNA in mice. The researchers then connected the different types of microRNA to distinct phases of the breast cycle. From similar experiments, scientists all over the globe mapped out the different types of microRNA involved with breast cancer [8]. Some types of microRNAs act as tumor suppressors, whereas others act as oncogenes and aid in tumor growth. Let7, a family of 12 tumor-suppressing microRNAs, inhibits the spread of cancer cells and represses key factors involved in the growth of cancer. MiR-125a and miR-125b suppress cell growth and favor apoptosis, the death of cells, in breast cancer by targeting the messenger RNA that encodes the RNAstabilizing protein HUR, which acts as a marker in breast cancer. However, this type of microRNA also has negative responses toward breast cancer and in some mammals, influences the growth of breast cancer [8]. FIGURE 3 [9] Summarizes the different types of microRNA involved with breast cancer. Although microRNAs fulfill the role of both oncogenes and tumor suppressor genes, scientists have yet to figure out whether cancer causes the microRNAs to behave in a certain manner or if the behavior is due to the cellular phenotype. Since microRNAs can regulate multiple targets and specify tissue expression, it is hard to classify them as just oncogenes or just tumor suppressors [7]. To explore the full therapeutic potential of microRNA, researchers first have to figure out how microRNA regulates gene expression. MECHANISMS OF BREAST CANCER PATHOLOGY As scientists research and experiment more with microRNAs, the more they believe that microRNAs act as promising biomarkers, a substance that indicates the presence of a disease, of early stage breast cancer. Active microRNAs can regulate gene expression by controlling the translation of messenger RNAs during the DNA replication process. Because the dysregulation of microRNAs is associated with cancer, microRNAs are in a position to serve as potential biomarkers for the diagnosis of breast cancer [10]. Unlike other detection methods, microRNAs can be easily detected in biopsies. They are found in body fluids, such as blood plasma (colorless fluid in the blood) and serum (protein-rich liquid that separates from the blood when it solidifies). Certain studies have shown that various types of microRNAs can distinguish breast cancer cells from healthy, normal cells [10]. Experiment on MicroRNA Profiling and Expression 3 Megha Murthy Shivani Tuli that a microRNA’s expression profile changes as a result of breast cancer. They compared the expression change result they calculated from the study with five other data sets and found similar results that supported their calculated results [10]. This study shows how the expression of microRNA relates to breast cancer. Different microRNA expressions showed different microRNA regulation patterns in breast cancer. This indicates that microRNA controls the gene expression of cancer and that certain types of microRNA either suppress the tumor or aid tumor growth. An upregulation expression change indicates that the microRNA contributes to cancer growth. A downregulation expression change indicates that the microRNA helps suppress tumors. Figure 5, below, identifies the gene regulation of several types of microRNAs. In one experiment at the Taizhou Central Hospital in China between 2012 and 2013, researchers focused on the profiling of microRNA expression associated with breast cancer by examining the microRNA expressions of several patients. The researchers accumulated fresh frozen breast cancer tumors, adjacent normal tissues, and preoperative serum from eight breast cancer patients who had undergone surgery but had not been treated with chemotherapy. For a control group, the researchers obtained a control serum sample from eight healthy females [10]. After gathering the materials, the researchers isolated the RNA (molecule responsible for coding through DNA sequencing, decoding, expression of genes and carrying the genetic code to the DNA) from each of the tissues and serum samples using a Trizol reagent, which helps extract the RNA. To eliminate biological variation, the researchers pooled similar samples. They collected the RNA from the tumor cells separately from the RNA from the tissue sample and the RNA from the healthy cells [10]. The researchers at this university then sequenced and aligned the RNA against a mature microRNA sequence and observed the correlation, using the Pearson correlation coefficient (the linear relationship or correlation between two variables), between the two groups. Those microRNAs with a q value (value after the data has been adjusted to exclude insignificant differences in the data) of 0.8 were labeled as significantly different from the rest of the microRNA [10]. FIGURE 5 [10] This figure shows some types of microRNAs regarding expression change. The ability of microRNAs to regulate gene expression has led to more research and studies about its potential in cancer treatment as well as the role it plays in differentiating between benign tumors and malignant tumors. THERAPEUTIC POTENTIAL OF MICRORNA IN BREAST CANCER Experimenting with a microRNA’s ability to regulate gene expression has led researchers and scientists to further conduct research on the therapeutic treatment associated with the different expressions of microRNAs. Based on the internal and external conditions at any given time, microRNAs can indicate which genes are actively expressed at a specific time. In a recent study exploring the biogenesis of microRNAs, researchers found out that patients with high levels of miR-21 expression were likely to have a poor therapeutic outcome. This study concluded that certain chemotherapeutic drugs might be more favorable depending on the particular microRNA expression [8]. In a recent Ted Talk, Jorge Soto explained the ability of microRNAs to easily detect breast cancer using their genetic expression. He praised microRNAs stating that the approach to detect cancer, “uses state-of-the-art molecular biology, a low-cost, 3D-printed device, and data science to try to tackle one of humanity's toughest challenges [11].” An individual FIGURE 4 [10] This figure depicts the correlation between the expression profiles of serum from breast cancer patients and those from healthy individuals (A) as well as the expression profiles of breast cancer tumors and normal tissues (B) Based on the high correlation between the breast cancer serum and normal control serum, as depicted in the figure above, the researchers, upon further examination, concluded that the microRNAs may be released into the serum selectively and the microRNA expression profile changes in the tumor and serum as a result of breast cancer [10]. To predict the targets of the expressed microRNAs, the researchers used an online database to obtain the target genes whose expression changes coincided with a p-value of less than or equal to 0.05 between the human breast cancer and normal human breast. A p-value less than 0.05 signifies that the results the researchers obtained is a significant indicator 4 Megha Murthy Shivani Tuli who believes he or she has breast cancer doesn’t even need to go to the hospital. In fact, they can go to their doctor and have an RNA molecule extracted from their blood. The lab technician extracting the RNA will place it on a plate which will look for a specific microRNA that corresponds to the extracted RNA expression. A smartphone is then placed onto the plate and connected to a computer. The phone takes several pictures and sends the pictures for interpretation and processing on the online database. Within a 60-minute time span, the database will match the extracted RNA with a specific microRNA and analyze how much microRNA is in the sample. The sample will then be compared to a specific microRNA pattern and soon will reveal the type of cancer the patient has [11]. The advantage of this method is that not only is it cheaper and less time consuming than current methods involving medical imaging, but it also detects the breast cancer in its earlier stages rather than when the cancer is classified as a stage 4 or stage 5. Even though research is still being done to detect cancer at an earlier stage, the ability of microRNAs to regulate genes will aid in finding a definite treatment to cancer. At various universities around the world, including the University of Pittsburgh, professors are conducting breast cancer research in their labs and researching the therapeutic potential of microRNAs. In fact, Professor Partha Roy from the University of Pittsburgh, Bioengineering Department at the Swanson School of Engineering stated that polypeptide chains and lipids that enclose microRNAs can cause target action on cancer cells and potentially treat cancer [12]. Antagomirs, chemically engineered oligonucleotides, involve microRNA modulation to treat breast cancer. In a study done with mice to test out antagomirs, researchers injected the antagomirs into the liver of the mouse. The researchers observed that the antagomir inhibited the expression of a type of microRNA in the liver [7]. Figure 6 depicts how an active antagomir blocks the microRNA in order to inhibit its oncogenic properties. FIGURE 6 [13] This figure shows how antagomirs can block microRNA. By inhibiting microRNA expression, antagomirs can essentially prevent microRNAs with oncogenic properties from spreading the tumor throughout the body. Although research is still being done on the microRNA’s potential in cancer treatment, additional research, as articulated in the article written by Sonia Melo, has shown that the use of microRNAs can sensitize tumors to chemotherapy. Currently, there is still no cancer treatment that is 100% effective against cancer. Although chemotherapy has been successful with some patients, some patients require multiple doses of chemotherapy treatment. The only problem with this is that the more sessions of chemotherapy the patient undergoes, the more the body resists the treatment. One of the few obstacles to a successful cancer treatment using chemotherapy is resistance to chemotherapy with increased chemotherapy exposure. MicroRNAs can alleviate this problem because of their ability to target multiple messenger RNA molecules involved in the signaling pathways that are damaged by cancer. Since multiple microRNAs can target a given gene, the successful outcome of microRNA therapy depends on the number of targets and the affinity of those targets to the microRNA. The microRNA has to target the appropriate gene based on its own expression in order to avoid unwanted side effects [14]. Overall, microRNAs have the potential of detecting and treating cancer. There are several treatment and detection methods involving microRNAs that enable certain genes to be either activated or suppressed depending on the gene expression of the individual microRNA. They can also aid in alleviating resistance to chemotherapy and essentially play a significant role in cancer therapy. ETHICAL CONCERNS ABOUT USING MICRORNAS Several ethics committees around the globe have approved of using microRNAs in cancer research and cancer treatment. However, there are still various factors to consider when working with microRNAs surrounding the ethics of the research. Arguments Against Using microRNAs to Treat Breast Cancer Currently, the use of microRNAs isn’t available for clinical applications. For them to be used in a clinical setting, there are certain limitations that medical authorities need to look into. Research has shown that an overexpression of microRNAs in the body is an acceptable indicator for the presence of breast cancer in the body. However, researchers need to determine the “normal” levels and diversity of microRNAs in body fluids. To determine how much 5 Megha Murthy Shivani Tuli microRNA accounts for overexpression, it’s important to indicate the normal amount of microRNAs in the body [7]. When looking at the diversity of microRNAs in the body, it’s important to account for factors such as race, gender, and age. The “normal” level of microRNA in a 50-year-old female might be different than the “normal” level of microRNA in an 18-year-old male. MicroRNA profiling approaches for body fluid samples has to be universal to ensure that there are no dramatic changes in the microRNA expressions [7]. Regarding microRNA expressions, when using antagomirs to inhibit specific microRNA expressions, it’s important to first understand which microRNAs correspond to which expressions. If an antagomir that inhibits a tumor suppressing microRNA is created, then using antagomirs to treat cancer will have the opposite effect. The antagomirs will advance the growth of the tumor since it just inhibited the microRNA that suppresses the growth of the tumor. In addition, antagomirs have only been tested on animals and not on humans. Scientists have yet to determine the effects of injecting antagomir into the human body. Since humans have an immune system, there is no way to tell yet whether the effects of antagomirs on the human body will be useful if human immune system fights the antagomirs [7] Although there are several concerns with using microRNAs in treatment, there are more concerns with actually conducting an experiment involving microRNAs. To get accurate results, the sample size has to be consistent with all the studies completed. Some experiments studied a small number of patients and healthy individuals, whereas other studies examined a large group of patients and a large control group. In this case, the statistical analysis per group will be different and there will be no basis to compare results. In a statistical study, it is always best to have a large sample choice to avoid significant differences in the data [15]. While preparing the sample used for microRNA detection, it’s important to be consistent with the extracted sample. Some experiments have extracted whole blood samples, or whole serum and plasma samples. Whole blood samples include different cell types, such as white blood cells, red blood cells, and platelets, which could alter the results and yield inaccurate results. In this case, it is better to use serum, which contains the liquid portion of blood mixed with the proteins, and plasma, which contains a liquid portion of blood along with proteins, some molecules, and some cells. However, these samples can affect the data as well, since there is a higher concentration of microRNAs in cells. There also appears to be a higher concentration of microRNA in serum than in plasma which would cause difficulties when comparing data with a different starting material. In data analysis, it is often difficult to choose a reference microRNA to compare results with [14]. Prior to the discovery of microRNAs’ therapeutic potential in cancer, scientists believed microRNAs were useless molecules in the body. However, after extensive research, scientists determined the microRNA’s ability to regulate genes in the body. This discovery has provided new opportunities for research as well as a new perspective towards gene expression. Not only are scientists looking at the gene expression of microRNAs, but they are looking at other genetically engineered molecules, such as antagomirs, that can potentially inhibit the negative effect of microRNA in the body. Discovering the true potential of microRNAs has allowed scientists and researchers to take a second look at other molecules they initially deemed as irrelevant in the body. This discovery will give medical professionals another chance to research a cure for a disease they initially had no cure or treatment for. MicroRNA research offers hope to patients with cancer and other “untreatable” diseases. Since microRNAs can target several genes at once, they can regulate several cancer genes at once on several different pathways. Data also indicates that several types of microRNAs, such as Let-7, yield successful results when it comes to suppressing tumors. This microRNA, especially, has shown, in numerous studies, that it reduces the proliferation of tumorous cells and increases the apoptotic activity of tumor cells. In the past decade, several types of microRNAs have been discovered and are awaiting clinical use. Although not every type of microRNA is approved for clinical use in the human body, some types have been approved for use on some animal models, such as mice. Once more research has been done on animal models, there is a chance that using microRNA to suppress tumors or for other research will be approved for clinical use in humans [16]. The therapeutic potential not only has its uses in treating cancer but also has useful applications in cancer stem cells. Cancer stem cells are defined as “a small fraction of cancer cells that have the ability to self-renew and give rise to identical daughter cells [16].” These cells are often labeled as the root cause of tumors and actually are more resistant to therapy than normal cancer cells. This is likely the reason why patients grow resistance to chemotherapy after prolonged exposure. Since various types of microRNAs express different patterns, it is highly likely that there are types of microRNA that can inhibit the spread of cancer stem cells. Discovering and conducting research on different types of microRNAs in the body will help prevent chemoresistance and increase the success rate of chemotherapy in patients [16]. Although there are various concerns about conducting research and the general ethics surrounding research, the positive effects of microRNA in preventing the spread of cancer and treating cancer outweigh those research concerns. FUTURE DIRECTIONS Positive Responses Toward Using MicroRNAs to Treat Breast Cancer As the most common type of cancer, breast cancer continues to affect millions of women worldwide. Although there are ways to detect and treat this disease, the success rate 6 Megha Murthy Shivani Tuli for available treatments isn’t as high as it could be. Current methods of detection and diagnosis including x-ray imaging, sonography machines, and mammograms, detect the disease at a very late stage when chemotherapy is the only treatment that has a chance of being successful. To solidify a definite treatment for cancer, cancer has to be detected at an earlier stage. MicroRNAs enable physicians to detect cancer at an earlier stage, giving them more time to find a better treatment with a higher success rate. Detecting cancer using microRNAs is as easy as getting a blood test. Not only are the results available in less than an hour, the process is also inexpensive. Apart from detecting cancer, microRNAs also have the potential to treat cancer based on the patterns of expression. Already, hundreds of types of microRNAs have been discovered, each with its own unique expression and pattern. Since each cancer is different, each type of microRNA can target different cancerous genes and manipulate them to stop spreading throughout the rest of the body. Since the discovery of microRNAs’ therapeutic potential towards treating breast cancer, additional research has been conducted on other molecules that may help treat other diseases. In fact, microRNAs don’t only help treat and detect cancer; they also have potential in treating other diseases, such as heart disease and Hepatitis. Although scientists haven’t fully ventured into the therapeutic potentials of microRNA to treat other diseases, there is a possibility, based on gene expression, that microRNA can cure other genetic diseases. Understanding how gene expression works and understanding the cellular pathways in the body will open up new opportunities for genetic research. The future seems bright for finding a cure for cancer with the discovery of microRNAs and similar molecules. In the future, the number of people who acquire cancer will hopefully decrease and within the next few decades, there most likely will be a better treatment for cancer involving the use of microRNAs rather than chemotherapy and other radiation inducing treatments. There is still a long way to go in cancer research, but with each passing day, there is a new discovery on how best to treat this disease. Scientists are working hard to find a cure and soon, with the help of microRNAs, cancer will be a curable and treatable disease. MicroRNAs can also treat cancer and increase the success rate of chemotherapy since several types of microRNAs can prevent resistance to chemotherapy. There are so many types of microRNAs out there that still need to be discovered that potentially have therapeutic properties and will benefit the public health. Before scientists began conducting research on the mechanisms of microRNAs, they believed these molecules to be insignificant molecules of the human body. However, after discovering that microRNAs play a significant role in the growth and suppression of pathogens, scientists, researchers, engineers, and other professionals involved in the medical field, sought out to explore the therapeutic and harmful effects of these small molecules. Medical authorities were most interested in the therapeutic potential of microRNA to detect and treat cancer. Finding a treatment to cancer would benefit several individuals, especially those who suffer from cancer or those who know others who either suffer from cancer or have passed away from cancer. Now that scientists know that microRNAs can regulate gene expression and can suppress or accelerate tumor growth, scientists can combine these abilities with drugs and multidrug therapy to create a more efficient treatment. Since many diseases are controlled by multiple pathways, microRNAs can target these multiple pathways because of their ability to target multiple genes simultaneously [17]. Combining the use of microRNA to combat cancer with drug therapy would make cancer treatment more effective because it would reduce the risk of several side effects of certain drugs. However, to combine the use of microRNA with drug therapy, scientists would have to experiment more with how drug treatment influences microRNA gene expression. By understanding the relationship between drug treatment and microRNA gene expression, scientists can pinpoint the most appropriate microRNAs to target based on whether they’re oncogenes or tumor suppressors. Depending on the type of microRNA, the drug will either aid the microRNA in suppressing the tumor or inhibit the microRNA from aiding in the spread of the tumor [17]. Once enough microRNA research has been conducted in laboratories, the practice can be used to clinics where it will be more widely accessible to people. Moving the practice to clinics will benefit the public health. MicroRNAs are considered a “top candidate for the next generation of biomarkers” [18] because they are more likely to lead to early detection of cancer than proteins or other molecules. MicroRNA biomarkers are also more likely to be discovered by genomic tools, which would make it easier to detect cancer earlier. As more appreciation grows for microRNA research, the more research scientists, researchers, and engineers can conduct to improve upon this technology and help save lives. Since there are several types of microRNAs in the body, each with their own unique gene expression, there is a possibility that several of these microRNAs have properties that will have therapeutic properties. Experimenting and Sustainability of MicroRNAs Sustainability involves providing health benefits and improving the quality of life. Defining a technology, such as microRNAs, as “sustainable” means improving human health. Using microRNAs to detect and treat cancer has to be safe and has to have a positive impact on the individual rather than a negative impact. MicroRNAs have the potential to improve the quality of life. 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Accessed 2.28.2017. ADDITIONAL SOURCES D. Lammey. Biology Lecture. B.Reed Henderson High School. 4.6.2016. L. Pappo. Statistics Lecture. B. Reed Henderson High School. 11-2013. ACKNOWLEDGEMENTS Megha Murthy would like to thank her dad for editing this paper and supporting her through the writing process. We would both like to thank our families for supporting us while writing this paper. We would also like to thank the Swanson School of Engineering for assigning this paper because it really helped improve our research paper writing skills. We would also like to thank our co-chair and chair for making sure we’re on the right path and checking up to make sure that we meet the deadline for this paper. 8
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