BackgroundmicroRNAs (miRNAs) can regulate the sensitivity of cancer cells to chemotherapy and radiotherapy. Aberrant expression of miR-195 has been found to be involved in colorectal cancer (CRC); however, its function and underlying mechanism in the radioresistance of CRC remains unclear.MethodsThe levels of miR-195 and CARM1 were detected by quantitative reverse transcription-polymerase chain reaction and Western blot analysis in HCT-116 and HT-29 cells, respectively. Colony survival and apoptosis were determined by clonogenic assay and flow cytometry analysis, respectively. The apoptosis-related proteins Bax, Bcl-2, and γ-H2AX were detected using Western blot. The targets of miR-195 were identified by bioinformatic prediction and luciferase reporter assays. CRC cells in vitro and in vivo were exposed to different doses of X-ray radiations.ResultsmiR-195 was downregulated, and CARM1 was upregulated in HCT-116 and HT-29 cells. miR-195 overexpression or CARM1 knockdown suppressed colony survival, induced apoptosis, promoted expression of Bax and γ-H2AX, and inhibited Bcl-2 expression in CRC cells. CARM1 was identified and validated to be a functional target of miR-195. Moreover, restored expression of CARM1 reversed the enhanced radiosensitivity of CRC cells induced by miR-195. Furthermore, miR-195 increased the sensitivity of CRC cells to radiation in vivo.ConclusionmiR-195 enhances radiosensitivity of CRC cells through suppressing CARM1. Therefore, miR-195 acts as a potential regulator of radioresistance for CRC cells and as a promising therapeutic target for CRC patients.
Long non-coding RNA HOXD-AS1 (HOXD cluster antisense RNA 1) has been demonstrated to be closely associated with the progression of several tumors. However, the biological function of HOXD-AS1 and the underlying molecular mechanism in gastric cancer are still unclear. The expression of HOXD-AS1 in gastric cancer cell lines was evaluated by quantitative real-time polymerase chain reaction. The association of HOXD-AS1 expression and clinical parameters was statistically analyzed by chi-square test. Cell viability, colony formation capacity, and phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 3 in treated SGC-7901 and BGC-823 cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, and western blot analysis, respectively. The results indicated that HOXD-AS1 was significantly upregulated in gastric cancer cells and clinically involved in tumor size, invasion depth, tumor-node-metastasis stages, regional lymph nodes, lymphatic metastasis, as well as distant metastasis. HOXD-AS1 knockdown dramatically inhibited gastric cancer cell proliferation, colony formation capacity, and phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 3 in vitro. In addition, HOXD-AS1 overexpression significantly promoted gastric cancer cell proliferation and colony formation capacity, whereas both Janus kinase small interfering RNAs and Janus kinase 2 inhibitor AG490 overturned these effects. Furthermore, xenograft assays confirmed the biological function of HOXD-AS1 in vivo. Taken together, our data elucidate that knockdown of HOXD-AS1 dramatically suppresses gastric cancer cell growth by inactivating the Janus kinase 2/signal transducer and activator of transcription 3 pathway in vitro and in vivo, contributing to a better understanding of gastric cancer pathogenesis and providing a possible theoretical foundation for long non-coding RNA-directed diagnosis and therapy against this disease.
Biliary tract cancer (BTC) is the second common cancer in liver cancer. Chemotherapy is the mainstay of treatments for patients with advanced or metastatic disease, while fluorouracil (FU)-based and gemcitabine (GEM)-based treatments are most widely applied. This NMA aimed to figure out whether the addition of platinum (PLA) and target agents (TAR) can influence the efficacy and safety of standard chemotherapy. Network meta-analysis (NMA) was conducted based on the records from PubMed, Embase and Cochrane. Eligible data was extracted from available qualified trials and outcomes. Software R 3.2.3 and STATA 13.0 were used to conduct the Bayesian NMA, calculating odds ratios (ORs) and hazard ratios (HRs) with 95% credible interval (CrI) to evaluate different treatments.Almost all treatments were superior to best supportive care (BSC) and FU in terms of 1-OS, 2-OS and 1-PFS. GEM+PLA and GEM+PLA+TAR exhibited better efficacy than most treatments in 1-OS, 2-OS and 1-PFS, and yielded better results than BSC and GEM+FU in terms of 2-PFS. Most drug-containing treatments reported higher overall response rate (ORR) than BSC. GEM and GEM+FU were associated with a higher risk of neutropenia and thrombocytopenia compared to FU, FU+PLA and GEM+PLA. No statistical difference was detected in terms of nausea and vomiting.GEM+PLA and GEM+PLA+TAR were both efficacious and were associated with fewer adverse events. In conclusion, the addition of PLA can significantly improve the efficacy of FU and GEM-based treatments, and the addition of TAR to GEM+PLA can contribute to further improvement, but with a mild increase of adverse events.
Abstract. The aim of the present study was to investigate the expression and function of forkhead box protein 3 (FOXP3) in gastric cancer using a rat model.
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