Auburn Research Day 2021

Cl i n i ca l Case Repor t | Med i ca l St udent Review of Risk Factors for Metastatic Spread of Signet Ring Cell Carcinoma of the Colon

Background: Colorectal cancer (CRC) is the most common type of cancer for both the male and female genders. A very rare type of colorectal cancer is signet ring cell carcinoma (SRCC), which is associated with a poor prognosis. SRCC is defined as a tumor in which more than 50% of cells contain intracellular mucin. It is proposed that long-going inflammation of the colon, possibly due to the western diet, is a major risk factor for CRC due to the occurrence rate in industrialized countries. Here we report a case of a 63-year- old Caucasian male with history of colon cancer with diagnosed metastatic disease of the liver and peritoneum. An in-situ evaluation of the decedent revealed multiple nodules adherent to the inner surface of the pleura. After further microscopic evaluation, it was determined the patient to have pulmonary metastatic spread of SRCC. Methods: Detailed review of 20 articles, cases and studies; discussing the risk factors of CRC, occurrence of SRCC, patterns of metastatic spread of CRC specifically SRCC and epidemiology of metastatic CRC. Caroline Houston, Brynn Hentschel, Alexys Ramos, David Stephen, DO Edward Via College of Osteopathic Medicine - Auburn 026

Results: SRCC patients commonly present at older ages with more advanced clinical stages than that of patients with mucinous adenocarcinoma (MAC), another subtype of CRC. MAC and SRCC more frequently metastasize to the peritoneum and less frequently to the liver when compared to more generic CRC. It is not uncommon to find a pleural metastasis listed with peritoneal metastasis. Multiple risk factors have been studied in regard to CRC and its metastasis. Conclusion: Colorectal cancer is often thought of as one disease, although there are differences in the geographic distribution, clinical presentation and risk factors associated. There is difficulty in determining what risk factors contribute to the progression of rare SRCC compared to generic CRC partly because there is not a clear line of difference between the metastatic spread colon and rectal cancers. Further understanding of SRCC is evident with the progression of medicine and the rise in the occurrence rate of CRC.

027 Clay E. Pandorf 1 , Nicole I. Anthony 2 and Joanna Sztuba-Solinska 2 1 Cell Biology and Physiology, Edward Via College of Osteopathic Medicine – Auburn; 2 Department of Biological Sciences, Auburn University B i omed i ca l Resea rch | Med i ca l Facu l t y Characterizing the Structure-to-Function Relationship of a Novel Antisense Long Non-Coding RNA Associated with the Type I/B Myosin Heavy Chain Gene of Skeletal and Cardiac Muscle for Potential Drug-Targeting

Muscle size, contractile phenotype and metabolism are subject to physiological regulation and determine strength, power and endurance capacity in skeletal muscle; and heart rate, stroke volume and cardiac output in cardiac muscle. Inactivity of muscle is the overarching consequence of disease, injury and lifestyle choices, and presents a serious challenge to outcomes of musculoskeletal health. Exercise capacity is a strong predictor of early morbidity and mortality and is grounded upon the state of health of the skeletal muscle and cardiovascular systems. At the center of all of these contributors to human health is the motor protein responsible for muscle contraction of slow (fatigue- resistant) skeletal and cardiac muscle, the slow-type I or β -myosin heavy chain (I/ β -MHC), encoded by the MYH7 gene. Decreased muscle activity results in a loss of I/ β -MHC that is mediated by the transcriptional repression of MYH7. We have identified a novel antisense (AS) long non-coding (lnc) RNA that overlaps MYH7. Sequencing determined that the first exon of this lncRNA, named MYH7-AS, overlaps miR208b. miR208b is a part of a network including miR208a and miR499, that have been shown to activate MYH7 by repressing the transcriptional repressors. Since MYH7-AS is partially complementary to miR208b, it reasons to hypothesize that MYH7 may regulate it. Investigations have revealed that MYH7 mRNA is significantly decreased after hindlimb muscle unloading as compared to ambulatory control rat soleus, and there is a corresponding 6.5-fold increase in MYH7-AS. Moreover, the negative relationship between MYH7 mRNA and MYH7-AS is maintained

(R2 = 0.81) in normal tissue when comparing the expression levels in rat soleus, left ventricle and right ventricle. These data are consistent with a regulatory relationship between MYH7AS and MYH7. In the next phase of this project, we endeavor to characterize the structure-to-function relationship of MYH7-AS, for potential therapeutic targeting. lncRNAs have been shown to act by regulating the expression of genes at the nidus of critical physiological and pathophysiological pathways, by either sequestering regulatory factors, or modulating the activity or localization of chromatin regulatory complexes. Identifying the MYH7-AS mode of action is, thus, expected to enhance knowledge related to MYH7 transcriptional regulation, aiding the development of new therapeutic targets to remedy myriad skeletal and cardiac muscle conditions. The central hypothesis is that MYH7-AS interactions with regulatory RNAs (i.e. micro RNAs) and proteins (i.e. chromatin remodeling complexes), mediate MYH7 repression. This pathway is hypothesized to facilitate regulation of contractile phenotype, myofiber size and metabolic properties of skeletal and cardiac muscle. Harnessing the combined power of the in vitro, in the cell and in vivo systems, we will 1) elucidate MYH7-AS RNA secondary structure, 2) map MYH7-AS interactions with cellular RNAs and proteins, 3) explore the druggability potential of MYH7-AS functional RNA motifs. The goal of this is to identify small molecule therapeutics that will induce myosin isoform switching by targeting MYH7-AS structure, and thus restore optimal muscle function.

21 2021 Via Research Recognit ion Day