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|Title:||RPS3 knockdown impedes survival, proliferation and metastasis of colon cancer CACO2 cells||Authors:||Maaliki, Lama||Advisors:||Nasr, Zeina||Subjects:||Colon cancer
Colon cancer is a major cause of death in the world accounting for around 9% of cancer incidence. It has been found that many ribosomal proteins (RPs), including RPS3 are overexpressed in colon adenocarcinomas and adenomatous polyps (Pogue-Geile et al., 1991)(Pogue-Geile et al., 1991)(Pogue-Geile et al., 1991)(Pogue-Geile et al., 1991)(PogueGeile et al., 1991)(Pogue-Geile et al., 1991)(Pogue-Geile et al., 1991). In addition to their role in ribosome biogenesis, RPs have also extraribosomal functions, ranging from DNA repair to replication, proliferation, apoptosis, and chemoresistance. The involvement of RPs in tumor onset and progression has been somewhat ignored despite their differential expression in many human cancers. Ribosomal protein S3 (RPS3), a DNA repair endonuclease, has been overexpressed in various human tumors, including colon adenocarcinoma. However, no report has characterized the involvement of RPS3 in tumor formation and progression in colon cancer. In this study, we propose to determine the expression level of RPS3 in a colon cancer cell line (Caco-2) compared to a normal colon cell line (NCM) before and after knockdown by siRNA. By looking at the effects of RPS3 knockdown on cell survival, apoptosis, proliferation, metastatic behavior and metabolism, we will start to understand the mechanism through which RPS3 exerts its tumorigenic functions. Our results suggest that RPS3 knockdown by siRNA decreased proliferation and survival of both cell lines, however the effect was more protruding in Caco2 cells. Results showed that RPS3 knockdown inhibited cell proliferation in Caco2 cells mostly at day 5 posttransfection as demonstrated by WST-1 cell proliferation assay and reduced survival by 2.5 folds. Furthermore, the migration and invasion ability of Caco2 cells was reduced by half after 24 hours and 2.5-fold after 72 hours, respectively, upon RPS3 knockdown in vitro. LDH activity in Caco2 cells also decreased after RPS3 knockdown suggesting a shift in the metabolism of the cells probably from aerobic glycolysis to aerobic respiration. These findings might present RPS3 as an attractive molecular marker and a potential target for colon cancer therapy.
Includes bibliographical references (p. 43-59).
Supervised by Dr. Zeina Nasr.
|URI:||https://scholarhub.balamand.edu.lb/handle/uob/4208||Rights:||This object is protected by copyright, and is made available here for research and educational purposes. Permission to reuse, publish, or reproduce the object beyond the personal and educational use exceptions must be obtained from the copyright holder||Ezproxy URL:||Link to full text||Type:||Thesis|
|Appears in Collections:||UOB Theses and Projects|
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