Colorectal adenocarcinoma is the third most common cancer worldwide. PARP6, a novel member of the poly(ADP-ribose) polymerases (PARPs) and survivin, a member of the family of inhibitor of apoptosis (IAP) proteins are associated with a poor prognosis in various types of cancers. However, limited evidence exists regarding the interaction between PARP6 and survivin in colorectal adenocarcinoma. In the present study, we used the paired samples of 20 patients with colorectal adenocarcinoma to detect the expression of PARP6 and survivin in both tumor and adjacent normal colorectal mucosa. Their interaction and roles in cell viability, cell cycle, cell apoptosis and cell invasion were further investigated. Our results showed that both PARP6 and survivin exhibited higher expression in colorectal adenocarcinoma tissues and SW620 cells when compared with levels in adjacent non-tumor tissues and a normal colon cell line FHC. Co-immunoprecipitation assay showed that a significant correlation existed between PARP6 and survivin. We also showed that sole treatment of PARP6 siRNA or survivin siRNA partially inhibited the cell survival and invasion, induced cell G0/G1 arrest, and cell apoptosis at the early and late stages. The combined treatment of PARP6 siRNA and survivin siRNA suppressed the cell survival and cell invasion, further induced cell cycle phase G0/G1 arrest, and cell apoptosis at the early and late stages. Taken together, knockdown of PARP6 or survivin promotes cell apoptosis and inhibits the cell invasion of colorectal adenocarcinoma cells. A significant correlation exists between PARP6 and survivin, and both are promising targets for the development of new strategies for the diagnosis and treatment of advanced or metastatic colorectal adenocarcinoma.

The efficacy of chemotherapy for colon cancer is limited due to the development of chemoresistance. MicroRNA (miR)-188-5p is downregulated in various types of cancer. The aim of the present study was to explore the molecular role of miR-188 in oxaliplatin (OXA) resistance. An OXA-resistant colon cancer cell line, SW480/OXA, was used to examine the effects of miR-188-5p on the sensitivity of colon cancer cells to OXA. The target of miR-188-5p was identified using a luciferase assay. Cell cycle distribution was also assessed using flow cytometry. The measurement of p21 protein expression, Hoechst 33342 staining and Annexin V/propidium iodide staining was used to evaluate apoptosis. The expression of miR-188-5p significantly increased in SW480/OXA compared with wild-type SW480 cells. The luciferase assay demonstrated that miR-188-5p inhibited Ras GTPase-activating protein 1 (RASA1; also known as p120/RasGAP) luciferase activity by binding to the 3'-untranslated region of RASA1 mRNA, suggesting that miR-188-5p could target RASA1. In addition, miR-188-5p downregulation or RASA1 overexpression promoted the chemosensitivity of SW480/OXA, as evidenced by increased apoptosis and G 1 /S cell cycle arrest. Moreover, RASA1 silencing abrogated the increase in cell apoptosis induced by the miR-188-5p inhibitor. The findings of the present study suggested that miR-188-5p could enhance colon cancer cell chemosensitivity by promoting the expression of RASA1.

Background: One main drawback of chemotherapy application in colon cancer clinically is drug resistance. miR-188-5p has been shown to be down-regulated in various types of cancer. The aim of this study was to explore the molecular mechanism of miR-188-5p in drug resistant cancer cells. Methods: we examined the effects of miR-188-5p on the sensitivity of colon cancer cells to oxaliplatin (OXA) by using SW480/OXA cell line. The target of miR-188-5p was determined by luciferase activity assay. The cell cycle distribution were detected by flow cytometry. The expression of p21, Hoechst 33342 staining and Annexin V assays were used to detect the cell apoptosis. Results: The expression of miR-188-5p was significantly increased in SW480/OXA cells compared with SW480 cells. By luciferase assay we found that miR-188-5p miRNA binds to RASA1 (Ras GTPase-activating protein 1, also known as p120RasGAP), and overexpression of miR-188-5p inhibited RASA1 expression by binding to the 3'-untranslated region of RASA1 mRNA. In addition, suppression of miR-188-5p enhanced the chemosensitivity of the oxaliplatin-resistant colon cancer cells. Furthermore, suppression of RASA1 abrogated the increasement of cell apoptosis induced by miR-188-5p inhibitor, while, overexpression of RASA1 induced cell apoptosis in SW480/OXA cells. Our results suggested that miR-188-5p played chemoresistant role in colon cancer through regulating RASA1 expression. Conclusion: The findings of our study suggest that target miR-188-5p is capable of enhancing the chemosensitivity of colon cancer cells by promoting RASA1.