Background:Expression of ABCG2 is normally absent or low in the pancreas, but high in human pancreatic cancer cells. The mechanism by which ABCG2 is altered in human cancers remains unknown.Methods:We investigated ABCG2 expression in four pancreatic cancer cell lines, and used three microRNA (miRNA) target prediction programmes, and information from the existing literature to predict and identify hsa-miR-520h as an miRNA that targets ABCG2. The function of this miRNA was investigated by transient transfection of the pancreatic cancer cell line PANC-1 with oligonucleotides that mimic hsa-miR-520h.Results:Results showed that both mRNA and protein levels of ABCG2 were reduced, indicating that it was a target of hsa-miR-520h. Introduction of hsa-miR-520h mimics into PANC-1 cells also resulted in inhibition of cell migration and invasion, and reduction of side population cells. Cell proliferation, cell cycle progression and apoptosis were not affected.Conclusions:We propose that the effects of hsa-miR-520h may be, at least in part, caused by its regulation of ABCG2. Thus, our findings provide a new insight into the function of miRNA in the regulation of ABCG2 expression in pancreatic cancer. Gene therapy using miRNA mimics may therefore be useful as a pancreatic cancer therapy.

Marital status is an independent prognostic factor for survival in several cancers. To determine if that is also true for pancreatic cancer after surgical treatment, we examined 13,370 cases of pancreatic cancer reported to the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2012. We found that patients who were widowed at the time of diagnosis were more likely to be female, a high percentage were elderly, a high ratio were diagnosed in early years, and a high proportion of tumors were located at the head of the pancreas (P < 0.05). Marital status was confirmed to be an independent prognostic factor in both univariate and multivariate analyses (P < 0.05). In those with localized disease, 5-year pancreatic cancer cause-specific survival was 6.5% lower in widowed patients than married ones (38.6% vs. 32.1%), though this difference was not significant in a multivariate analysis (P = 0.084). In those with regional disease or distant metastasis, univariate and multivariate analyses indicated marital status to be an independent prognostic factor (P < 0.05). Thus marital status is an important prognostic factor in pancreatic cancer, and widowed patients are at greater risk of death than others.

A meta-analysis was conducted to evaluate the association between duration of oral contraceptive use and risk of hypertension. Relevant studies published in English or Chinese were identified by a search of PubMed, Web of Science, Wanfang Database, and China National Knowledge Infrastructure to January 2017. Seventeen articles containing 24 studies with 270,284 participants were included in this meta-analysis.The pooled relative risk of hypertension for the highest vs lowest category of oral contraceptive duration was 1.47 (95% confidence interval, 1.25-1.73), and excluding three studies with a relative risk >3.0 yielded a pooled relative risk of 1.26 (95% confidence interval, 1.11-1.44). A linear dose-response relationship was found (P nonlinearity =0.69) and the risk of hypertension increased by 13% (relative risk, 1.13; 95% confidence interval, 1.03-1.25) for every 5-year increment in oral contraceptive use. The duration of oral contraceptive use was positively associated with the risk of hypertension in this meta-analysis.

Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Though studies have implicated the roles of microRNAs in pancreatic cancer progression, little is known about the role of miR-613 in pancreatic cancer. In the present study, the expression of miR-613 was down-regulated in pancreatic cancer tissues and cancer cell lines. Down-regulation of miR-613 was positively correlated with tumor differentiation, advanced TNM stage, nodal metastasis and shorter overall survival in patients with pancreatic cancer. Overexpression of miR-613 suppressed cell proliferation, invasion and migration, and induced cell apoptosis and cell cycle arrest at G0/G1 phase in pancreatic cancer cells. Bioinformatics analysis, luciferase reporter assay and rescue experiments showed that notch3 was a direct target of miR-613. MiR-613 was inversely correlated with notch3 expression in pancreatic cancer tissues. The long non-coding RNA, HOX transcript antisense RNA (HOTAIR) was up-regulated in both pancreatic cancer tissues and cancer cell lines, and HOTAIR suppressed the expression of miR-613 via functioning as a competing endogenous RNA. In vivo studies showed that stable overexpression of miR-613 or knock-down of HOTAIR suppressed tumor growth and also reduced the expression of notch3. In conclusion, these results suggest that HOTAIR functions as a competing endogenous RNA to regulate notch3 expression via sponging miR-613 in pancreatic cancer.

Pancreatic cancer is one of the most malignant tumors that are difficult to diagnose at its early stage and there is no effective therapy. Recent studies uncovered that many non-protein-coding RNAs including the class of long noncoding RNAs (lncRNAs) are differentially expressed in various types of tumors and they are potent regulators of tumor progression and metastasis. LncRNA can mediate tumor initiation, proliferation, migration and metastasis through modulating epigenetic modification, alternative splicing, transcription, and protein translation. In this review, we discuss the molecular mechanism of lncRNAs in the involvement of tumor growth, survival, epithelial-mesenchymal transition, tumor microenvironment, cancer stem cells and chemoresistance in pancreatic ductal adenocarcinoma (PDAC).

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Abstract. Oleuropein could inhibit growth and/or induce apoptosis in several cancer cell lines. In this study, we investigate how oleuropein strongly induces apoptotic cell death in HeLa human cervical carcinoma cells. Oleuropein induced HeLa cells apoptosis as demonstrated by induction of a sub-G 1 peak in flow cytometry and apoptosis-related morphological changes observed by fluorescence microscopy after being stained by Hoechst 33324. The results also showed that 150 -200 mM oleuropein-treated HeLa cells were arrested at the G 2 /M phase. Western blot analysis revealed that the phosphorylated ATF-2, c-Jun NH 2 -terminal kinase (JNK) protein, p53, p21, Bax, and cytochrome c protein in the cytoplasm significantly increased in a dose-dependent manner after treatment of oleuropein for 24 h. Additionally, increasing levels of Bax in response to JNK/SPAK signaling, which formed mitochondrial membrane channels, accounted for releasing of cytochrome c and activation of caspase-9 and -3. SP600125 (20 mM), a JNK 1/2 inhibitor, markedly suppressed the formation of apoptotic bodies and JNK activation induced by oleuropein at 200 mM. Thus, oleuropein-induced apoptosis was activated by the JNK/SPAK signal pathway. The result shows that oleuropein holds promise as a potential chemotherapeutic agent for the treatment of HeLa cells.

Under malignant circumstances, PaSCs express and secret galectin-1, which could further promote the proliferation and invasion of cancer cells.