Circular RNA ciRS-7 promotes the proliferation and metastasis of pancreatic cancer by regulating miR-7-mediated EGFR/STAT3 signaling pathway

Background: Pancreatic ductal adenocarcinoma(PDAC) is the most deadly type of tumor, and its pathogenesis remains unknown. Circular RNAs(circRNAs) may be functional and bind to micro RNAs and consequently, influence the activity of targeted mRNAs. Recent researches indicate that one circRNA, ciRS-7, acts as a sponge of miR-7 and thus, inhibits its activity. It is well known that miR-7 is a cancer suppressor in many cancers. However, the relationship between ciRS-7 and miR-7, and the role of ciRS-7 in PDAC, remains to be elucidated. Methods: miR-7 and ciRS-7 expression in 41 pairs of PDAC tumors and their paracancerous tissues were detected by quantitative reverse transcription polymerase chain reaction(qRT-PCR). The relationships between their expression levels and clinicopathological features in PDAC tissues were assessed. The relationship between miR-7 and ciRS-7 was also assessed by Spearman’s correlation. We also used cell lines to evaluate the role of ciRS-7 in cell line behavior. The ciRS-7 interfere RNA(si RNA) and its empty vector were transfected into PDAC cells. PDAC cells proliferation and invasion abilities were detected by MTT assay and invasion analysis. The expression of proteins was assessed by Western blotting. Results: ciRS-7 expression was significantly higher in PDAC tissues than paracancerous tissues( P = 0.002). However, miR-7 expression showed the opposite trend( P = 0.048). Moreover, ciRS-7 expression was inversely correlated with miR-7 in PDAC( r s =-0.353, P = 0.023). ciRS-7 expression was also significantly elevated in venous invasion(3.72 ± 2.93 vs. 2.14 ± 1.26;P = 0.028) and lymph node metastasis(4.19 ± 2.75 vs. 2.32 ± 1.90;P = 0.016) in PDAC patients. Furthermore, ciRS-7 knockdown suppressed cell proliferation and invasion of PDAC cells( P < 0.05), and the downregulation of ciRS-7 resulted in miR-7 overexpression and subsequent inhibition of epidermal growth factor receptor(EGFR) and signal transducer and activator of transcription 3(STAT3). Conclusions: Circular RNA ciRS-7 plays an oncogene role in PDAC, partly by targeting miR-7 and regulating the EGFR/STAT3 signaling pathway.

The effect of adjuvant chemotherapy in resectable cholangiocarcinoma: A meta-analysis and systematic review

Background: The benefit of adjuvant chemotherapy for resectable cholangiocarcinoma remains unclear due to the lack of randomized control studies. This study aimed to investigate the possible benefit of postoperative adjuvant chemotherapy for resectable cholangiocarcinoma. Data sources: Relevant research articles published before 1 st March 2018 in Pub Med, Embase and the Cochrane library databases were retrieved. Published data were extracted and analyzed by RevMan 5.3, and the results were presented as hazard ratios(HRs) [95% confidence intervals(CI)] and forest plots. Results: One prospective and eighteen retrospective studies were included, with a total number of 11,458 patients, 4696 of whom received postoperative chemotherapy. There was a significant improvement of the overall survival(OS) for patients who underwent operation + adjuvant chemotherapy compared to those who underwent operation alone(HR = 0.61; P < 0.001). Subgroup analyses show that the postoperative chemotherapy group compared with operation alone group are indicated as follows: hilar cholangiocarcinoma group(HR = 0.60; P < 0.001), intrahepatic cholangiocarcinoma group(HR = 0.60; P < 0.001), R1 resection group(HR = 0.71; P = 0.04), LN-positive diagnosis group(HR = 0.58; P < 0.001), gemcitabine-based chemotherapy group(HR = 0.42; P < 0.001), distal cholangiocarcinoma group(HR = 0.48; P = 0.17), R0 resection group(HR = 0.69; P = 0.43), and 5-flurouracil-based chemotherapy group(HR = 0.90; P = 0.66), respectively. Conclusions: Postoperative adjuvant chemotherapy can improve the OS in intrahepatic and hilar cholangiocarcinoma patients. However, distal cholangiocarcinoma patients gain no benefit from postoperative adjuvant chemotherapy. Prospective randomized trials are warranted in order to define the standard chemotherapy regimen.