miR-200b-3p mitigates oxaliplatin resistance via targeting TUBB3 in colorectal cancer.

BACKGROUND: Numerous abnormally expressed miRs have been reported involved in oxaliplatin (L-OHP) resistance of colorectal cancer (CRC). The present study aimed to investigate whether miR-200b-3p could regulate L-OHP resistance via targeting TUBB3 in CRC cells. METHODS: L-OHP resistant HT29 and HCT116 cells were exposed to escalating concentrations of L-OHP up to 30 µm. The effect of miR-200b-3p on L-OHP resistant CRC cells was then evaluated using the cell counting kit-8 (CCK-8) assay. CRC cell apoptosis was detected using Annexin V-FITC/PI double staining. Bioinformatics algorithms and luciferase reporter assays were also performed to investigate whether TUBB3 was a direct target of miR-200b-3p. RESULTS: miR-200b-3p declined in L-OHP resistant CRC tissues and cell lines, and the overexpression of miR-200b-3p elevated the L-OHP sensitivity in L-OHP resistant HT29 and HCT116 cells. In addition, we determined the potential mechanisms underlying miR-200b-3p-mediated reversal of L-OHP resistance by mediating its downstream target TUBB3, and the overexpression of miR-200b-3p could induce migration and growth inhibition and apoptosis in L-OHP resistant HT29 and HCT116 cells by silencing ßIII-tubulin protein expression. However, the overexpression of TUBB3 reversed miR-200b-3p mimic-induced migration, as well as growth inhibition and apoptosis, in L-OHP resistant CRC cells. CONCLUSIONS: miR-200b-3p improved L-OHP resistance and induced growth inhibition and cell apoptosis in L-OHP resistant CRC cells, and the underlying mechanism was mediated, at least partially, through the suppression of ßIII-tubulin protein expression.

Upregulation of microRNA-370 promotes cell apoptosis and inhibits proliferation by targeting PTEN in human gastric cancer.

Growing evidence suggests that microRNA plays an essential role in the development and metastasis of many tumors, including gastric cancer. Aberrant miR­370 expression has been indicated in tumor growth, but the mechanism of miR­370 inhibits both the proliferation and metastatic ability for gastric cancer remains unclear. Accumulating evidence reported that PTEN signaling pathway plays an important role in the cellular processes, such as apoptosis, cell growth and proliferation. The goal of this study was to identify whether miR­370 could inhibit the growth, migration, invasion, proliferation and metastasis of gastric cancer through targeting PTEN. Real-time PCR (RT-PCR) was used to quantify miR-370 expression in vitro experiments. The biological functions of miR­370 were determined via cell proliferation. Our study indicated that miR­370 targeted PTEN leading to activation of apoptosis signaling and the cell proliferation of cervical cancer cells, ameliorating gastric cancer growth and progression. In addition, the combination of miR­370 and PTEN inactivated AKT, MDM2 and mTOR while stimulated caspase-3, p53 and GSK3ß expression, promoting apoptosis and suppressing proliferation of gastric cancer cells. Therefore, our study revealed the mechanistic links between miR­370 and PTEN in the pathogenesis of gastric cancer through modulation of cell apoptosis and proliferation. Additionally, targeting miR­370 could serve as a novel strategy for future gastric cancer therapy clinically.

Peptic Ulcer Disease in Healthcare Workers: A Nationwide Population-Based Cohort Study.

Health care workers (HCWs) in Taiwan have heavy, stressful workloads, are on-call, and have rotating nightshifts, all of which might contribute to peptic ulcer disease (PUD). We wanted to evaluate the PUD risk in HCWs, which is not clear. Using Taiwan's National Health Insurance Research Database, we identified 50,226 physicians, 122,357 nurses, 20,677 pharmacists, and 25,059 other HCWs (dieticians, technicians, rehabilitation therapists, and social workers) as the study cohort, and randomly selected an identical number of non-HCW patients (i.e., general population) as the comparison cohort. Conditional logistical regression analysis was used to compare the PUD risk between them. Subgroup analysis for physician specialties was also done. Nurses and other HCWs had a significantly higher PUD risk than did the general population (odds ratio [OR]: 1.477; 95% confidence interval [CI]: 1.433-1.521 and OR: 1.328; 95% CI: 1.245-1.418, respectively); pharmacists had a lower risk (OR: 0.884; 95% CI: 0.828-0.945); physicians had a nonsignificantly different risk (OR: 1.029; 95% CI: 0.987-1.072). In the physician specialty subgroup analysis, internal medicine, surgery, Ob/Gyn, and family medicine specialists had a higher PUD risk than other physicians (OR: 1.579; 95% CI: 1.441-1.731, OR: 1.734; 95% CI: 1.565-1.922, OR: 1.336; 95% CI: 1.151-1.550, and OR: 1.615; 95% CI: 1.425-1.831, respectively). In contrast, emergency physicians had a lower risk (OR: 0.544; 95% CI: 0.359-0.822). Heavy workloads, long working hours, workplace stress, rotating nightshifts, and coping skills may explain our epidemiological findings of higher risks for PUD in some HCWs, which might help us improve our health policies for HCWs.