Research Paper Volume 12, Issue 11 pp 10544—10555

Long noncoding RNA LINC00460 conduces to tumor growth and metastasis of hepatocellular carcinoma through miR-342-3p-dependent AGR2 up-regulation

Han Hong1, *, , Chengjun Sui2, *, , Tao Qian3, *, , Xiaoyong Xu1, , Xiang Zhu1, , Qiang Fei1, , Jiamei Yang2, , Minhui Xu1, ,

  • 1 Department of Hepato-Pancreato-Biliary Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, China
  • 2 Department of Special Treatment I and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China
  • 3 Department of General Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China
* Equal contribution

Received: January 15, 2020       Accepted: April 28, 2020       Published: June 3, 2020
How to Cite

Copyright © 2020 Hong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor in the world. It ranks third among cancer-induced deaths worldwide and has the characteristics of high metastasis and high recurrence rate. Long non-coding RNA (LncRNA) LINC00460 is significantly up-regulated in multiple types of cancers and is closely related to the progression of tumors. However, effects of LINC00460 and corresponding regulatory path in HCC are still poorly investigated.

In our study, we found that expression of LINC00460 was up-regulated in HCC tissues and cell lines compared with the control. Then we revealed that knockdown of LINC00460 suppressed cell proliferation and cell mobility and induced cell apoptosis in HCC cells. Further study demonstrated that knockdown of LINC00460 suppressed the progression of HCC by elevating the expression of microRNA (miRNA, miR)-342-3p. Besides that, metastasis marker, Anterior gradient homolog 2 (AGR2) was found to be a target of miR-342-3p and overexpression of AGR2 promoted the progression of HCC. Finally, the in vivo experiments further verified the anti-tumor effects of LINC00460 / miR-342-3p / AGR2 axis in HCC.

The LINC00460 / miR-342-3p / AGR2 axis exerts anti-tumor effect in HCC in vitro and in vivo, consolidating and expanding the research about targeted gene therapy for early diagnosis and treatment of HCC.


HCC: Hepatocellular carcinoma; LncRNA: Long non-coding RNA; qRT-PCR: Quantitative real-time polymerase chain reaction; miRNA: MicroRNA; AGR2: Anterior gradient homolog 2; IHC: Immunohistochemistry; EMT: epithelial to mesenchymal transition; mRNAs: messenger RNAs; ceRNA: Competitive endogenous RNA.