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Research Paper|Volume 12, Issue 17|pp 17681—17693

Long non-coding RNA Loc490 inhibits gastric cancer cell proliferation and metastasis by upregulating RNA-binding protein Quaking

Zhengxi He1,2,3,4, Zhaojun Duan5, Ling Chen6, Bin Li1,7, Yanhong Zhou1,2,3,4
  • 1Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China
  • 2Basic School of Medicine, Cancer Research Institute, Central South University, Changsha 410008, Hunan, People’s Republic of China
  • 3Hunan Cancer Hospital, The Affiliated Tumor Hospital of Xiangya Medical College, Central South University, Changsha 410008, People’s Republic of China
  • 4Key Laboratory of Carcinogenesis of the Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Ministry of Education, Cancer Research Institute, Central South University, Changsha 410008, People’s Republic of China
  • 5Medical Research Center, Key Laboratory of Cancer Proteomics of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China
  • 6Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China
  • 7National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China
Received: February 21, 2020Accepted: July 14, 2020Published: September 15, 2020
https://doi.org/10.18632/aging.103876

Copyright: © 2020 He 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.

Abstract

Gastric cancer (GC) is one of the most common malignant tumor types worldwide. Long non-coding RNAs (lncRNAs) have important epigenetic effects, including altering the proliferation and metastasis of malignant tumors. We used gene chip technology to search for lncRNAs that were differentially expressed in GC and metastatic lymph node tissues compared with adjacent normal tissues. The lncRNA Loc490 and the RNA-binding protein Quaking (QKI) were downregulated in GC tissues and lymph node metastases compared with normal tissues, and the levels of these two genes correlated positively with one another. Loc490 expression correlated negatively with lymph node metastasis and vein/nerve invasion, while it correlated positively with overall and disease-free survival. In vitro, Loc490 post-translationally enhanced the expression of QKI and suppressed the expression of epithelial-mesenchymal transition-related molecules. Overexpression of Loc490 inhibited GC cell proliferation, invasion and metastasis and exerted strong antitumor effects in vivo, while silencing of QKI antagonized these effects. A potential binding site between Loc490 and QKI was detected through bioinformatics analysis and confirmed through RNA immunoprecipitation and mutant analyses. Our results suggest that lncRNA Loc490 inhibits GC cell proliferation and metastasis by upregulating RNA-binding protein QKI.