Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2022; 14(1): 253-264
Published online Jan 15, 2022. doi: 10.4251/wjgo.v14.i1.253
Lnc524369 promotes hepatocellular carcinoma progression and predicts poor survival by activating YWHAZ-RAF1 signaling
Wei Zheng, Guo-Liang Shen, Ke-Yang Xu, Qiao-Qiao Yin, Tian-Chen Hui, Zhe-Wen Zhou, Cheng-An Xu, Shou-Hao Wang, Wen-Hao Wu, Ling-Fei Shi, Hong-Ying Pan
Wei Zheng, Department of Clinical Medicine, Medical College of Soochow University, Suzhou 215006, Jiangsu Province, China
Wei Zheng, Qiao-Qiao Yin, Hong-Ying Pan, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Guo-Liang Shen, Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Ke-Yang Xu, School of Chinese Medicine, Hongkong Baptist university, Hong Kong 999777, China
Tian-Chen Hui, Zhe-Wen Zhou, Department of Graduate School, Bengbu Medical College, Bengbu 233030, Anhui Province, China
Cheng-An Xu, Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
Shou-Hao Wang, Wen-Hao Wu, Medical Department of Qingdao University, Qingdao University, Qingdao 266071, Shandong, China
Ling-Fei Shi, Diagnosis and Treatment Center of Osteoporosis, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hang Zhou 310014, Zhejiang Province, China
Author contributions: Zheng W designed the report and wrote the paper; Hui TC, Yin QQ, Zhou ZW, Xu CA, and Shi LF performed the majority of experiments and analyzed the data; Wu WH and Wang SH performed the molecular investigations; Shen GL designed and coordinated the research; Xu KY and Pan HY revised the paper.
Supported by the Medical and Health Science and Technology Project of Zhejiang Province (No. 2021KY043) and Chinese Foundation for Hepatitis Prevention and Control-TianQing Liver Disease Research Fund Subject (No. TQGB2020168).
Institutional review board statement: This study was reviewed and approved by the Zhejiang Provincial People’s Hospital Ethics Committee.
Informed consent statement: All patients in our study provided informed consent.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hong-Ying Pan, MD, Chief Doctor, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou 310014, Zhejiang Province, China. hypanhz@139.com
Received: June 22, 2021
Peer-review started: June 22, 2021
First decision: July 4, 2021
Revised: July 28, 2021
Accepted: September 16, 2021
Article in press: September 16, 2021
Published online: January 15, 2022
Processing time: 202 Days and 19.4 Hours
Abstract
BACKGROUND

Liver cancer is one of the most highly malignant cancers, characterized by easy metastasis and chemoradiotherapy resistance. Emerging evidence indicates that long noncoding RNAs (LncRNAs), including Lnc524369, are highly involved in the initiation, progression, radioresistance, and chemoresistance of hepatocellular carcinoma (HCC). However, the function of Lnc524369 remains unclear.

AIM

To explore the function of Lnc524369 in HCC.

METHODS

To investigate the effect of Lnc524369, tissue from 41 HCC patients were analyzed using CCK8, migration, and invasion assays. Lnc524369 and YWHAZ (also named 14-3-3ζ) mRNA were detected by qPCR, and YWHAZ and RAF1 proteins were detected by western blot in liver cancer cell lines and human HCC tissues. The Cancer Cell Line Encyclopedia (CCLE) databases, STRING database, Human Protein Atlas database, and the TCGA database were used for bioinformatic analysis.

RESULTS

Lnc524369 was significantly upregulated in the nucleus of liver cancer cells and human HCC tissues. Overexpression of Lnc524369 was associated with the proliferation, migration, and invasion of liver cancer cells. YWHAZ and RAF1 proteins and YWHAZ mRNA were overexpressed in liver cancer, which could be attenuated by overexpression of Lnc524369. Lnc524369 and its downstream target YWHAZ and RAF1 proteins were negatively associated with overall survival time.

CONCLUSION

Lnc524369 might be a promising target of HCC as it can enhance liver cancer progression and decrease the overall survival time of HCC by activating the YWHAZ/RAF1 pathway.

Keywords: Long noncoding RNAs; Lnc524369; Hepatocellular carcinoma; YWHAZ; RAF1

Core Tip: Lnc524369 is expressed at low levels in the cytoplasm but enriched in the nucleus of hepatocellular carcinoma (HCC) cells and might be strongly coexpressed with YWHAZ. Overexpression of Lnc524369 promoted the proliferation, migration, and invasion of liver cancer cells. The Lnc524369-mediated YWHAZ/RAF1 pathway was negatively associated with the overall survival time of HCC patients.