Knockdown of lncRNA LINC01234 Suppresses the Tumorigenesis of Liver Cancer via Sponging miR-513a-5p

Wen Xu; Kesang Li; Changfeng Song; Xiaotong Wang; Yueqi Li; Baixue Xu; Xin Liang; Wanli Deng; Junqing Wang; Jianwen Liu

doi:10.3389/fonc.2020.571565

Knockdown of lncRNA LINC01234 Suppresses the Tumorigenesis of Liver Cancer via Sponging miR-513a-5p

Front Oncol. 2020 Oct 16:10:571565. doi: 10.3389/fonc.2020.571565. eCollection 2020.

Authors

Wen Xu¹, Kesang Li^{2

3}, Changfeng Song¹, Xiaotong Wang¹, Yueqi Li¹, Baixue Xu¹, Xin Liang¹, Wanli Deng⁴, Junqing Wang⁵, Jianwen Liu¹

Affiliations

¹ State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
² Department of Hematology and Oncology, Hwa Mei Hospital, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China.
³ Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China.
⁴ Department of Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁵ Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Background: Liver cancer is a frequent malignancy with poor prognosis and high mortality all over the world. It has been reported many lncRNAs could modulate the tumorigenesis of liver cancer. To identify novel potential targets for liver cancer, the differential expressed lncRNAs between liver cancer and adjacent normal tissues was analyzed with bioinformatics tool.

Methods: The differential expressed lncRNAs between liver cancer and adjacent normal tissues were analyzed with bioinformatics tool. Cell viability and proliferation was tested by CCK8 and Ki67, respectively. Apoptosis of liver cancer cells was tested by flow cytometry. Gene and protein expressions in liver cancer cells were measured by qRT-PCR and western blot, respectively. In vivo model of liver cancer was established to detect the effect of LINC01234 on liver cancer in vivo.

Results: LINC01234 was found to be negatively correlated with the survival rate of patients with liver cancer. Moreover, knockdown of LINC01234 significantly suppressed the proliferation and invasion of liver cancer cells via inducing the apoptosis. Meanwhile, miR-513a-5p was sponged by LINC01234, and USP4 was found to be a direct target of miR-513a-5p. In addition, LINC01234 knockdown inhibited the tumorigenesis of liver cancer via inactivating TGF-β signaling. Furthermore, silencing of LINC01234 notably inhibited the tumor growth of liver cancer in vivo.

Conclusion: Downregulation of LINC01234 could inhibit the tumorigenesis of liver cancer via mediation of miR-513a-5p/USP4/TGF-β axis. Thus, LINC01234 might serve as a new target for the treatment of liver cancer.

Keywords: LINC01234; TGF-β; USP4; liver cancer; miR-513a-5p.