Background Colon cancer (CRC) is the second leading cause of cancer-related death, and its 5-year survival rate is very low. Homologous recombination repair (HRR) is deficient in most colon cancer. Some long non-coding RNAs (lncRNAs) participate in tumorigenesis of colon cancer through the HRR pathway. We aim to establish a prognostic model based on the HRR-related lncRNAs, expecting to provide a new strategy for precision treatment development in colon cancer. Methods Pearson’s correlation was used to identify the HRR-related prognostic lncRNAs in the TCGA-COAD cohort. The TCGA-COAD cohort was randomized into the training set and the testing set. LASSO Cox regression was used to establish the model which was analyzed in the training set and validated in the testing set and the entire TCGA-COAD cohort. Finally, we explored the potential biological function of our model. Results A prognostic model was established based on nineteen HRR-related lncRNAs in the training set. COAD patients were scored by the uniform formula and divided into high-risk and low-risk groups based on the median risk score. Patients with high-risk scores indicated poor prognosis in the training set, and the result was confirmed in the testing set and the entire TCGA-COAD cohort (all p < 0.01). Multivariable analysis suggested that our model was an independent factor for overall survival in COAD. The area under the curve (AUC) and C-index indicated that our model had better predictive efficiency than other indicators in the TCGA-COAD cohort. Functional enrichment analysis suggested that our model was associated with the MAPK pathway in COAD. Besides, our model was positively correlated with the HRD scores. Conclusion A new prognostic model was established based on nineteen HRR-related lncRNAs which had excellent predictive efficiency on the prognosis of COAD. This prognostic model may provide a new strategy for prognostic prediction of COAD patients.
Colorectal carcinoma (CRC) is the second most frequent cancer worldwide. MiR-491-3p, a tumor-suppressive microRNA (miRNA, miR), has been revealed to be abnormally expressed in CRC tissues. Meanwhile, up-regulated ubiquitous mitochondrial creatine kinase (uMtCK) contributes to CRC cell proliferation. Here we aim to explore whether aberrant miR-491-3p expression promotes CRC progression through regulating uMtCK. To this end, miR-491-3p and uMtCK levels were assessed in CRC tissues using quantitative real-time PCR (qRT-PCR). The biological roles of miR-491-3p and uMtCK in regulating CRC growth were evaluated using colony formation assay and mouse Xenograft tumour model. We found that miR-491-3p expression was decreased in CRC tissues compared with matched para-cancerous tissues, whereas uMtCK expression was increased. Functionally, miR-491-3p overexpression repressed SW480 cell growth, whereas miR-491-3p depletion accelerated SW620 cell proliferation and growth. Inversely, uMtCK positively regulated CRC cell proliferation. Mechanistically, miR-491-3p post-transcriptionally downregulated uMtCK expression by binding to 3’-UTR of uMtCK. Consequently, restoring uMtCK expression markedly eliminated the role of miR-491-3p in suppressing CRC growth. Collectively, miR-491-3p functions as a tumour suppressor gene by repressing uMtCK, and may be a potential target for CRC treatment.
Abstract. We investigated the expression of micro ribonucleic acid (miR)-20a-5p and its target gene, breast cancer metastasis suppressor 1 like (BRMS1L), in colon cancer tissues and their effects on the proliferation and apoptosis of colon cancer cells. The dual luciferase assay was used to detect the targeted regulation of miR-20a-5p on BRMS1L. The expression levels of miR-20a-5p and BRMS1L in colon cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). MiR-20a-5p mimic and mimic negative control (NC) were transfected into the colon cancer cell line SW480 by the liposome transient transfection method. The MTT assay, monoclonal formation of cancer cells, and flow cytometry were used to detect cell proliferation and apoptosis. The expres-sion level of miR-20a-5p in colon cancer tissues was significantly higher than that in adjacent tissues, and the expression level of BRMS1L was significantly lower than that in adjacent tissues. The expression level of miR-20a-5p was significantly correlated with tumor-node-metastasis (TNM) stage, lymph node metastasis, in-vasion depth, and differentiation degree. The higher the expression level of miR-20a-5p, the more advanced the TNM stage and invasion depth, and the easier it is for lymph nodes to metastasize (p<0.05). Compared with the control and the miR-NC groups, the miR-20a-5p group’s cell proliferation ability, expression of CyclinD1 and B-cell lymphoma-2 (Bcl-2) were significantly increased, while apoptosis ability and caspase-3 protein expression were significantly decreased (p<0.05). The expression of miR-20a-5p in colon cancer tissues and cells in-creased. Overexpression of miR-20a-5p could promote the proliferation of colon cancer cells and inhibit their apoptosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.