Oncotarget

Research Papers:

This article has been retracted. Retraction in: Oncotarget. 2024; 15:814-814.

MicroRNA-34a regulates liver regeneration and the development of liver cancer in rats by targeting Notch signaling pathway

Xiao-Ping Wang, Jian Zhou, Ming Han, Chuan-Bao Chen, Yi-Tao Zheng, Xiao-Shun He and Xiao-Peng Yuan _

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:13264-13276. https://doi.org/10.18632/oncotarget.14807

Metrics: PDF 2378 views  |   HTML 3762 views  |   ?  


Abstract

Xiao-Ping Wang1,*, Jian Zhou1,*, Ming Han1, Chuan-Bao Chen1, Yi-Tao Zheng1, Xiao-Shun He1, Xiao-Peng Yuan1

1Third Division of Organ Transplant Center, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P. R. China

*These authors have contributed equally to this work

Correspondence to:

Xiao-Peng Yuan, email: [email protected]

Keywords: microRNA-34a, liver regeneration, liver cancer, Notch signaling pathway

Received: August 19, 2016     Accepted: December 13, 2016     Published: January 25, 2017

ABSTRACT

Objective: This study aimed to investigate the role of microRNA-34a (miR-34a) in regulating liver regeneration (LR) and the development of liver cancer in rats by targeting Notch signaling pathway.

Methods: Thirty male Sprague-Dawley (SD) rats were randomly assigned into partial hepatectomy (PH) group and sham hepatectomy (SH) group. Hematoxylin and eosin (HE) staining was used to observe the histological change in liver tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels. Dual-luciferase reporter gene assay was performed to examine whether miR-34a targeted Notch1 gene. Human liver cancer Huh7 cells were transfected and divided into blank, negative control (NC), miR-34a mimics and miR-34a inhibitors groups. MTT and flow cytometry were used to detect cell growth, and cell cycle and apoptosis, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied detect to the expressions of miR-34a and Notch receptor mRNA. Western blotting was performed to detect the protein expressions of Notch receptors, P21, Bax, Bcl-2 and Bcl-xL. Tumor xenograft in nude mice was done to observe tumor formation in different groups.

Results: Compared to the SH group, miR-34a expression in liver tissues in the PH group decreased first and then increased to the normal level during LR. In early stage of LR, the expressions of Notch receptors and miR-34a were negatively correlated. Compared to the blank and NC groups, the cell growth was inhibited, cell cycle was mainly arrested in the G2/M phase and cell apoptosis rate increased in the miR-34a mimics group. Moreover, the expressions of miR-34a, P21 and Bax were up-regulated, while the expressions of Notch receptors, and Bcl-2 and Bcl-xL were down-regulated in this group. Additionally, the tumor growth in the miR-34a mimics group was reduced. The miR-34a inhibitors group showed contrary tendencies.

Conclusion: Our study demonstrates that miR-34a regulated LR and the development of liver cancer by inhibiting Notch signaling pathway.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 14807