miR‑448 targets Rab2B and is pivotal in the suppression of pancreatic cancer

Jin,Jing; Wu,Yingsheng; Zhou,Dongkai; Sun,Qiang; Wang,Weilin

doi:10.3892/or.2018.6562

miR‑448 targets Rab2B and is pivotal in the suppression of pancreatic cancer

Authors:
- Jing Jin
- Yingsheng Wu
- Dongkai Zhou
- Qiang Sun
- Weilin Wang
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Affiliations: Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: July 12, 2018 https://doi.org/10.3892/or.2018.6562
Pages: 1379-1389
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Improvements in survival rates for pancreatic cancer have been slow and the morality rate continues to increase in patients. MicroRNA (miR)‑448 is reported to be significantly downregulated in several types of cancer. In this study, Rab2B is target of miR‑488 was confirmed by bioinformatics analysis and validated using a luciferase reporter assay. A total of 72 cases of pancreatic cancer in patients diagnosed at The First Affiliated Hospital, School of Medicine, Zhejiang University (Hangzhou, China) were enrolled, and cancer specimens and their adjacent normal tissues were collected for analysis. The expression levels of miR‑448 and Rab2B in these tissues and in pancreatic cancer cell lines were quantified using reverse transcription‑polymerase chain reaction analysis. miR‑448 overexpression was achieved by cell transfection. Protein expression was assessed using western blot analysis. Cell viability, cell cycle and apoptosis were analyzed using CCK‑8 assay and flow cytometry, respectively. The results revealed a negative correlation between miR‑448 and Rab2B in the pancreatic tissues and cell lines. The results of bioinformatics analysis indicated that miR‑448 directly targeted Rab2B. Aberrant miR‑448 levels in PANC‑1 cells downregulated the expression of Rab2B, and significantly decreased cell proliferation and promoted apoptosis of cancer cells. It was also found that miR‑448 mimics resulted in G0/G1 cell cycle arrest and affected the expression of cell cycle regulators, including cyclin D1, p21 and p27. In addition, the miR‑448 mimics led to inactivation of the Akt/Mammalian target of rapamycin signaling pathway. The miR‑448 mimics induced apoptosis and activated the expression of caspase‑3, caspase‑9 and poly(ADP‑ribose) polymerase. The results suggested that miR‑448 was a negative regulator of Rab2B and promoted cell cycle arrest and apoptosis in pancreatic cancer.

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