miR-92b-3p Regulates Cell Cycle and Apoptosis by Targeting CDKN1C, Thereby Affecting the Sensitivity of Colorectal Cancer Cells to Chemotherapeutic Drugs

Abstract

Colorectal cancer (CRC) is the third most common malignant tumor in the world and the second leading cause of cancer death. Multidrug resistance (MDR) has become a major obstacle in the clinical treatment of CRC. The clear molecular mechanism of MDR is complex, and miRNAs play an important role in drug resistance. This study used small RNAomic screens to analyze the expression profiles of miRNAs in CRC HCT8 cell line and its chemoresistant counterpart HCT8/T cell line. It was found that miR-92b-3p was highly expressed in HCT8/T cells. Knockdown of miR-92b-3p reversed the resistance of MDR HCT8/T cells to chemotherapeutic drugs in vitro and in vivo. Paclitaxel (PTX, a chemotherapy medication) could stimulate CRC cells to up-regulate miR-92b-3p expression and conferred cellular resistance to chemotherapeutic drugs. In studies on downstream molecules, results suggested that miR-92b-3p directly targeted Cyclin Dependent Kinase Inhibitor 1C (CDKN1C, which encodes a cell cycle inhibitor p57Kip2) to inhibit its expression and regulate the sensitivity of CRC cells to chemotherapeutic drugs. Mechanism study revealed that the miR-92b-3p/CDKN1C axis exerted a regulatory effect on the sensitivity of CRC cells via the regulation of cell cycle and apoptosis. In conclusion, these findings showed that miR-92b-3p/CDKN1C was an important regulator in the development of drug resistance in CRC cells, suggesting its potential application in drug resistance prediction and treatment.

Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy

“…In addition, its expression at T0 was significantly associated with PFS. Although no data are available about miR-92b-3p dysregulation in cutaneous melanoma, this miRNA has been reported to function as an oncomiR in different types of malignancies and to promote chemoresistance [ 42 , 43 , 44 , 45 , 46 ]. miR-485-3p was downregulated in both T0/NRs vs. T0/Rs and TP/Rs vs. T0/Rs.…”

MicroRNAs (miRNAs): Novel potential therapeutic targets in colorectal cancer

“…Zhao et al. ( 98 )found that miR-92b-3p was highly expressed by CRC HCT8/T cells and that knockdown of miR-92b-3p may attenuate the resistance of MDR HCT8/T cells to chemotherapy in vitro and in vivo . They further demonstrated that miR-92b-3p regulated the sensitivity of CRC cells to chemotherapeutic drugs by regulating the cell cycle and apoptosis (via directly targeting cyclin-dependent kinase inhibitor 1C and suppressing its expression).…”

miR‑let‑7c‑3p targeting on Egr‑1 contributes to the committed differentiation of leukemia cells into monocyte/macrophages

“…They are endogenous small RNAs with a length of 18-24 nucleotides. Usually, they can base pair with the 3' untranslated region (UTR) of target mRNAs and silence genes at the post-transcriptional level by inhibiting mRNA translation or directly causing mRNA degradation and abnormal expression often appears in the occurrence and development of tumors (29). Among which the miRNA (MiR)-let-7 family is downregulated in various types of tumor tissues and has been widely studied as a tumor suppressor gene (30,31).…”