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Objective:To investigate the effect of miR-485-5p on cisplatin resistance of colon cancer cells through the PI3K/Akt-PAK1 signaling pathway.Methods:The LoVo/DDP cell lines were constructedand divided into an NC group(without transfection treatment), an miR-485-5p mimics group(transfected with miR-485-5p mimics), an miR-485-5p inhibitors group(transfected with miR-485-5p inhibitors), an IPA-3 group(intervention with IPA-3)and an miR-485-5p mimics+ IPA-3 group(transfection with miR-485-5p mimics andinterventionwith IPA-3), with all given 0, 3, and 5 μmol/L cisplatin treatment.Results:Among the 20 patients, the proportion of negative miR-485-5p detection was 85.0%(17/20), and the proportion of positive detection was 15.0%(3/20); the proportion of negative PAK1 detection was 20.0%(4/20), and the proportion of positive detection was 80.0%(16/20). The expression of miR-485-5p in colon cancer tissue was significantly lower than that in adjacent tissues( P<0.05); the expression of miR-485-5p in the human colon cancer cell lines LoVo, SW620, HCT116, and SW480 was all lower than in normal intestinal mucosal cells( P<0.05); the expression of miR-485-5p in LoVo/DDP was significantly lower than inLoVo( P<0.001). Under the action of 3 μmol/L and 5 μmol/L cisplatin, LoVo/DDP had highercell viability but a lower apoptosis rate than LoVo( P<0.001). The cell survival rate in the miR-485-5p mimics group was significantly lower than that in the miR-485-5p inhibitors group( P<0.001). Compared with the NC mimics group, overexpression of miR-485-5p significantly down-regulated luciferase activity of the wild-type PAK1 reporter gene( P<0.001); P-PI3k, P-Akt and PAK1levels in the miR-485-5p mimics group were significantly lower than in the miR-485-5p inhibitors group( P<0.001); the cell survival rate in the miR-485-5p mimics group, the IPA-3 group and the miR-485-5p mimics+ IPA-3 group was significantly lower than in the NC group( P<0.001)and the cell survival rate in the miR-485-5p mimics+ IPA-3 group was significantly lower than in the miR-485-5p mimics group( P<0.001). Conclusions:Up-regulation of miR-485-5p reverses colon cancer cisplatin resistance through the PI3K/Akt-PAK1signaling pathway, suggesting that overexpression of miR-485-5p or inhibition of the PI3K/Akt-PAK1signaling pathway enhances the therapeutic efficacy of cisplatin in colon cancer.
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Objective:To explore the effects of miR-485-5p on cisplatin-resistant ovarian cancer cells and it’s mechanism.Methods:RT-qPCR was used to detect the expression of miR-485-5p in human normal ovarian epithelial cell line (IOSE-80) and ovarian cancer cell lines (A2780,SKOV3,OVCAR3,OVCA433) . Cisplatin (DDP) -resistant ovarian cancer cells were constructed and the expression of miR-485-5p and EGFR was detected. CCK8 assay was used to detect cell proliferation ability in each group. Cell apoptosis was measured by flow cytometry.Results:Compared with IOSE-80 cell, miR-485-5p expression was decreased in each ovarian cancer cell lines, while the expression of EGFR was increased (all P<0.05) .The expression of miR-485-5p in SKOV3/DDP cell lines was further decreased while EGFR expression was further increased than that in SKOV3 cells ( P<0.05) . Transfection of miR-485-5p mimic into SKOV3/DDP cells could inhibit cell proliferation and induce apoptosis, but the results were reversed when cells were transfected with miR-485-5p inhibitor (all P<0.05) . The proliferation was increased while apoptosis was decreased in EGFR transfected SKOV3/DDP cells, but this effects was partially offseted by miR-485-5pmimic. Conclusion:miR-485-5p participates in the regulation of cisplatin resistance of ovarian cancer cells, and overexpression of miR-485-5p can promote the chemosensitivity of ovarian cancer, which may be achieved through negative regulation of EGFR.
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BACKGROUND: Papillary thyroid cancer (PTC) is the most common malignancy of all thyroid cancers. LncRNA LINC00460 has been proved to play roles in the oncogenesis and progression of various tumors, including papillary thyroid cancer. However, the potential molecular mechanism of LINC00460 in PTC is poorly investigated. RESULTS: LINC00460 was upregulated in PTC tissues and cells. Raf1 was upregulated in PTC tissues, but miR-485-5p was down-regulated. High LINC00460 expression was associated with poor prognosis. LINC00460 knockdown suppressed proliferation, migration, invation and EMT of PTC cells. Bioinformatics prediction revealed that LINC00460 had binding sites with miR-485-5p, which was validated by luciferase reporter assay. In addition, miR-485-5p was confirmed to directly target Raf1 3'-UTR. Moreover, LINC00460 promoted PTC progression by sponging miR-485-5p to elevate the expression of Raf1. Knockdown of LINC00460 restrained tumor growth in vivo. CONCLUSION: LINC00460 induced proliferation, migration, invation and EMT of PTC cells by regulating the LINC00460/miR-485-5p/Raf1 axis, which indicated that LINC00460 may be a potential biomarker and therapeutic target for PTC.