Association of microRNA-23b-3p down-regulation with progression and survival in pancreatic duct adenocarcinoma and its prospective function via bioinformatics analysis

作者：Liu, Jianghua; Li, Jianjun; Chen, Gang; Cai, Xiaoyong; Huang, Yubin; Li, Chunjun; Gan, Xiaoning; Wei, Danming; Dang, Yiwu^*; Luo, Dianzhong^*

来源：International Journal of Clinical and Experimental Pathology, 2016, 9(7): 6645-6658.

• Pancreatic duct adenocarcinoma (PDAC)
• MiR-23b-3p
• disease specific survival (DSS)
• prognosis
• real time RT-qPCR

Background: MicroRNAs (miRNAs) have been reported in various human malignancies, which play important roles in tumorigenesis and progression, acting as oncogenes or tumor suppressors. However, the role of miR-23b-3p in pancreatic duct adenocarcinoma (PDAC) is to be elucidated. The goal of this study was to explore the association of miR-23b-3p expression with clinic features in PDAC formalin-fixed, paraffin embedded (FFPE) tissues and survival in PDAC patients and to investigate the prospective function of miR-23b-3p via bioinformatics analysis. Methods: The expression of miR-23b-3p was detected in 57 PDAC and 25 adjacent normal pancreatic tissues (ANT), also in five PDAC cell lines and an immortal pancreatic epithelium cell line HPDE6c-7 by qRT-PCR. The relationship between miR-23b-3p level and clinicopathological parameters including survival of PDAC patients was analyzed with Spearman correlation, Kaplan-Meier method and Cox proportional hazards mode, respectively. In addition, the validated target genes of miR-23b-3p gathered from DIANA-TarBase v7.0 and miRTarBase 6.0 were assessed with Gene Ontology (GO) and KEGG pathway enrichment analyses. Results: The relative level of miR-23b3p was significantly lower in PDAC compared to ANT (P=0.0053). Remarkably lesser expression of miR-23b-3p was also found in capan-1, aspc1 and panc-1 PDAC cells, compared with HPDE6c-7 cell line, respectively (all P<0.05). Furthermore, miR-23b-3p expression level was significantly correlated with tumor size (r=0.341, P=0.001), depth of invasion (r=0.264 P=0.048) and tumor stage (r=0.281, P=0.034). Kaplan-Meier analysis displayed that patients with lower miR-23b-3p expression presented a poorer disease specific survival (DSS) (P=0.036). Additionally, multivariate analysis revealed that down-expression of miR-23b-3p, as well as the histological grade and tumor stage, was an independent predictor of DSS of PDAC. A total of 173 validated targets were collected and they had enriched GO terms in different pathways. KEGG enrichment analysis revealed that the validated targets of miR-23b3p were significantly enriched in some well-known oncogenic pathways of malignancies, including the pathway of "Pancreatic cancer" with the genes of E2F1, RAF1, JAK1, RB1, BCL2L1, CHUK and RAD51. Conclusion: MiR-23b-3p might become as a potential indicator related to progress and prognosis via targeting various key pathways in PDAC.

• 出版日期2016
• 单位广西医科大学