Emerging studies indicated that cancer stem cells represent a subpopulation of cells within the tumor that is responsible for chemotherapeutic resistance. However, the underlying mechanism is still not clarified yet. Here we report that miR-196b-5p is dramatically upregulated in CRC tissues and high expression of miR-196b-5p correlates with poor survival in CRC patients. Moreover, recurrent gains (amplification) contribute to the miR-196b-5p overexpression in CRC tissues. Silencing miR-196b-5p suppresses spheroids formation ability, the fraction of SP cells, expression of stem cell factors and the mitochondrial potential, and enhances the apoptosis induced by 5-fluorouracil in CRC cells; while ectopic expression of miR-196b-5p yields an opposite effect. In addition, downregulation of miR-196b-5p resensitizes CRC cells to 5-fluorouracil in vivo. Our results further demonstrate that miR-196b-5p promotes stemness and chemoresistance of CRC cells to 5-fluorouracil via targeting negative regulators SOCS1 and SOCS3 of STAT3 signaling pathway, giving rise to activation of STAT3 signaling. Interestingly, miR-196b-5p is highly enriched in the serum exosomes of patients with CRC compared to the healthy control subjects. Thus, our results unravel a novel mechanism of miR-196b-5p implicating in the maintenance of stem cell property and chemotherapeutic resistance in CRC, offering a potential rational registry of anti-miR-196b-5p combining with conventional chemotherapy against CRC.
Large intergenic non-coding RNA ribonucleic acids-ROR (lincRNA-ROR) has been reported to exert impacts on the maintenance of induced pluripotent stem cells and embryonic stem cells, and play important roles in human hepatocellular cancer. It contributes to tumorigenesis and metastasis and functions as a competing endogenous RNA (ceRNA) by sponging miR-145 in breast cancer. However, its clinical significance and prognostic value in colon cancer remain unknown. The aim of the present study was to clarify the clinicopathological role and prognostic value of lincRNA-ROR and miR-145 in colon cancer. In the present study, qRT-PCR was performed to measure the expression levels of lincRNA-ROR in colon cancer tissues and cell lines. Then, the clinicopathological significance and prognostic value of lincRNA-ROR were analyzed. LincRNA-ROR expression correlated with pT stage, pN stage, AJCC stage and vascular invasion. Knockdown of lincRNA-ROR restored the expression of miR-145, and had a significant influence on colon cancer cell proliferation, migration and invasion. Patients of the high lincRNA-ROR/low miR-145 group had significantly poorer outcomes than those of the low lincRNA-ROR/high miR-145 group. Taken together, Overexpression of lincRNA-ROR combined with depletion of miR-145 may exert crucial impact on colon cancer prognosis evaluation and treatment.
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