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.
BackgroundOur aim was to investigate the influence of FTS on human cellular and humoral immunity using a randomized controlled clinical study in esophageal cancer patients.MethodsBetween October 2013 and December 2014, 276 patients with esophageal cancer in our department were enrolled in the study. The patients were randomized into two groups: FTS pathway group and conventional pathway group. The postoperative hospital stay, hospitalization expenditure, and postoperative complications were recorded. The markers of inflammatory and immune function were measured before operation as well as on the 1st, 3rd, and 7th postoperative days (POD), including serum level of interleukin-6 (IL-6), C-reactive protein (CRP), serum globulin, immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA) and lymphocyte subpopulations (CD3 lymphocytes, CD4 lymphocytes, CD8 lymphocytes and the CD4/CD8 ratio) in the patients between the two groups.ResultsIn all, 260 patients completed the study: 128 in the FTS group and 132 in the conventional group. We found implementation of FTS pathway decreases postoperative length of stay and hospital charges (P < 0.05). In addition, inflammatory reactions, based on IL-6 and CRP levels, were less intense following FTS pathway compared to conventional pathway on POD1 and POD3 (P < 0.05). On POD1 and POD3, the levels of IgG, IgA, CD3 lymphocytes, CD4 lymphocytes and the CD4/CD8 ratio in FTS group were significantly higher than those in control group (All P < 0.05). However, there were no differences in the level of IgM and CD8 lymphocytes between the two groups.ConclusionsFTS improves postoperative clinical recovery and effectively inhibited release of inflammatory factors via the immune system after esophagectomy for esophageal cancer.Trial registrationChiCTR-TRC-13003562, the date of registration: August 29, 2013.
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