Abstract. microRNAs (miRNAs) are a class of small non-coding RNAs that post-transcriptionally regulate gene expression. Increasing evidence has shown that the deregulation of miRNAs is linked to cancer. The overexpression of miR-224 has been reported in several human cancers. The aim of the present study was to investigate the function of miR-224 in the pathogenetic process of hepatocellular carcinoma (HCC), and the precise mechanism underlying its function. Both gain-of-function and loss-of function assays were conducted through transfection with miR-224 mimics and miR-224 inhibitors in the HepG2 liver carcinoma cell line. The data revealed that miR-224 exerts a significant role in promoting cell proliferation, migration and invasion. Western blot analysis showed that the phosphorylation levels of AKT positively correlated with endogenous levels of miR-224. In addition, results from a dual luciferase reporter assay showed that the expression of the serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A β isoform (PPP2R1B) is inhibited by miR-224; thus, it appears that PPP2R1B is a candidate target of miR-224 in HCC. These data suggest that miR-224 plays a significant role in HCC, possibly through the activation of the AKT signaling pathway by targeting PPP2R1B.

Extrahepatic cholangiocarcinoma (EHCC) is a refractory malignancy with poor prognosis due to its early invasion, metastasis and recurrence after operation. Therefore, understanding the mechanisms of invasion and metastasis is the key to the development of new and effective therapeutic strategies for EHCC. In the present study we demonstrated that miR-221 promoted EHCC invasion and metastasis through targeting PTEN and formed a positive feedback loop with β-catenin/c-Jun signaling pathway. We found miR-221 was upregulated in EHCC specimens and CC cell lines. Moreover, miR-221 was found strongly associated with the metastasis and prognosis of EHCC patients. The expression of PTEN was downregulated in EHCC patients and CC cell lines, and was further demonstrated as one of the downstream targets of miR-221. In addition, our data indicated that β-catenin activated miR-221 through c-jun, while miR-221 enhanced β-catenin signaling induced-epithelial-mesenchymal transition (EMT) by targeting PTEN, hence forming a positive feedback loop in EHCC cell lines. In conclusion, our results suggested that miR-221 promotes EMT through targeting PTEN and forms a positive feedback loop with β-catenin/c-Jun signaling pathway in EHCC.

The study aimed to investigate the risk factors of postpancreatectomy hemorrhage (PPH) after pancreaticoduodenectomy (PD). A retrospective analysis of 423 patients who underwent PD between January 2008 and January 2014 was conducted. The overall incidence and all-cause mortality of PPH were 9.9% (42/423) and 2.1% (9/423), respectively. Independent risk factors of early PPH were revascularization (odds ratio (OR) = 6.786; 95% confidence interval (95% CI): 1.785–25.792; P = 0.005), history of abdominal surgery (OR = 5.009; 95% CI: 1.968–12.749; P = 0.001), and preoperative albumin levels (OR = 4.863; 95% CI: 1.962–12.005; P = 0.001). Independent risk factors of late PPH included postoperative pancreatic leakage (OR = 4.696; 95% CI: 1.605–13.740; P = 0.005), postoperative biliary fistula (OR = 6.096; 95% CI: 1.575–23.598; P = 0.009), postoperative abdominal infection (OR = 4.605; 95% CI: 1.108–19.144; P = 0.036), revascularization (OR = 9.943; 95% CI: 1.900–52.042; P = 0.007), history of abdominal surgery (OR = 8.790; 95% CI: 2.779–27.806; P < 0.001), and preoperative albumin levels (OR = 5.563; 95% CI: 1.845–16.776; P = 0.002).

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The present study aimed to explore the long non-coding RNA (lncRNA) expression profiles and correlation of lnc-PKD2-2-3 with tumor features and prognosis, and to investigate its effect on regulating cancer-cell stemness and its potential as a cancer stem cell (CSC) marker in cholangiocarcinoma (CCA). lncRNA expression profiles were determined in 3 pairs of CCA tumors and adjacent tissues by microarray analysis, and lnc-PKD2-2-3 expression was then validated in 60 paired samples by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Expression of common CSC markers [(CD44, CD133 and octamer-binding transcription factor 4 (OCT4)], CD44 + CD133 + cell proportions, sphere formation efficiency and drug resistance to 5-fluorouracil (5-FU) were measured following ectopic overexpression of lnc-PKD2-2-3 or silencing via small hairpin RNA lentivirus transfection into the TFK-1 and Huh-28 CCA cell lines. Finally, lnc-PKD2-2-3 expression was measured in CCA stem-like cells and normal CCA cells. The results from the microarray analysis identified a total of 4,223 upregulated and 4,596 downregulated lncRNAs between CCA tumor tissue and paired adjacent tissue, which were enriched in regulating cancer-associated pathways. RT-qPCR validation revealed that lnc-PKD2-2-3 was upregulated in CCA and associated with a higher Eastern Cooperative Oncology Group performance score, poor differentiation, advanced TNM stage, increased carcinoembryonic antigen and poor overall survival in CCA patients. In vitro , lnc-PKD2-2-3 increased CD44, CD133 and OCT4 expression as well as the CD44 + CD133 + cell proportion, raised the sphere formation efficiency and enhanced drug resistance to 5-FU in TFK-1 and Huh-28 cells. In addition, lnc-PKD2-2-3 was positively correlated with CSC markers in CCA tumor tissues and was markedly upregulated in CCA stem-like cells compared with that in normal CCA cells. In conclusion, lnc-PKD2-2-3, selected by lncRNA expression profiling, was associated with pejorative tumor features and poor prognosis, enhanced cancer stemness and may serve as a CSC marker in CCA.