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High Expression of LINC01268 is Positively Associated with Hepatocellular Carcinoma Progression via Regulating MAP3K7

Authors Jin X, Fu WX, Li D, Wang N, Chen J, Zeng Z, Guo J, Liu H, Zhong X, Peng H, Yu X, Sun J, Zhang X, Wang X, Xu B, Lin Y, Liu J, Kutter C, Li Y

Received 4 December 2020

Accepted for publication 22 February 2021

Published 8 March 2021 Volume 2021:14 Pages 1753—1769

DOI https://doi.org/10.2147/OTT.S295814

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Nicola Silvestris


Xiuli Jin,1 Weixin Fu,2 Dan Li,1 Ningning Wang,1 Jiayu Chen,1 Zilu Zeng,1 Jiaqi Guo,1 Hao Liu,3 Xinping Zhong,3 Hu Peng,4 Xin Yu,5 Jing Sun,1 Xinhe Zhang,1 Xue Wang,1 Beibei Xu,1 Yingbo Lin,6 Jianping Liu,4 Claudia Kutter,7 Yiling Li1

1Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2Science Experiment Center of China Medical University, Shenyang, 110122, People’s Republic of China; 3Department of Hepatobiliary Surgery, First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 4Emergency Department, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 5Department of Human Anatomy, School of Basic Medicine, Dali University, Dali, Yunnan, 671003, People’s Republic of China; 6Department of Oncology-Pathology, Karolinska Institute, Stockholm, 17177, Sweden; 7Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institute, Stockholm, 17177, Sweden

Correspondence: Claudia Kutter
Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institute, Stockholm, 17177, Sweden
Email [email protected]
Yiling Li
Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China
Email [email protected]

Objective: As one of the most common neoplastic diseases, hepatocellular carcinoma (HCC) has a high morbidity and mortality, which seriously threatens human health and places a heavy burden on society and medical care. At present, effective early diagnosis, prognosis and treatment of HCC are limited. Altered gene expression patterns of lncRNA are associated with the occurrence, development and prognosis of various malignancies, including HCC. The aim of this study was to investigate the correlation between the expression of LINC01268 and HCC, and to elucidate the potential underlying molecular mechanism.
Methods: Expression level and localization of LINC01268 in human liver cancer cells and HCC tissues were investigated using RT-qPCR and fluorescent in situ hybridization (FISH), respectively. Correlation of expression levels of LINC01268 and MAP3K7 with differentiation and poor overall patient survival of HCC were analyzed using in house collected and publicly available HCC tissue data. RT-qPCR and Western blot were applied to inspect the effects of depletion and overexpression of LINC01268 on MAP3K7 expression. HCC cell proliferation and apoptosis were also investigated by simultaneous overexpression of LINC01268 and knockdown of MAP3K7, in order to delineate that MAP3K7 is a downstream effector of LINC01268.
Results: In this study, we identified that LINC01268 was highly expressed in HCC cell lines and tissues. High LINC01268 expression level was associated with lower HCC nodule number, moderate/poor differentiation and poor overall survival. Knockdown of LINC01268 inhibited the proliferation of HCC cells, which was enhanced by overexpression of LINC01268. Co-expression analysis implied an interaction between LINC01268 and MAP3K7. Similar to LINC01268, MAP3K7 was highly expressed in HCC cells, and positively correlated with moderate/poor differentiation as well as poor prognosis. Knockdown of LINC01268 in HCC cell lines led to reduction of MAP3K7 at both mRNA and protein levels. Phenotypic effects due to LINC01268 overexpression in HCC cells were reversed by knockdown of MAP3K7.
Conclusion: Taken together, the abnormal high expression of LINC01268 is associated with HCC progression via regulating MAP3K7, suggesting LINC01268 as a novel marker for HCC prognosis and potentially a new therapeutic target.

Keywords: LINC01268, MAP3K7, hepatocellular carcinoma, proliferation, prognosis

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