Lnc-MUC20-9 binds to ROCK1 and functions as a tumor suppressor in bladder cancer.

Abstract

The study aimed to investigate the expression and function of bladder cancer (BC) long noncoding RNAs (lncRNAs) using a high-throughput platform. High-throughput sequencing was used to compare the expression profiles of lncRNA in BC and adjacent normal tissues. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), in situ hybridization, gene ontology, and Kyoto Encyclopedia of Genes and Genomes analysis were performed to verify differential expression of lncRNA. The effect of lncRNA overexpression on cellular proliferation, apoptosis, migration, and invasion was analyzed following the transfection of lncRNA overexpressing lentivirus into 5637 and T24 cell lines. The overexpressing cells were subcutaneously injected into nude mice to evaluate their effects on tumor growth. Tumor-associated RNA-binding proteins of lncRNA were analyzed by RNA pull-down combined with mass spectrometry. A total of 93 lncRNA genes were upregulated and 352 lncRNA genes were downregulated in the tissues of patients with BC. Of which, we investigated the function of downregulated lnc-MUC20-9. Overexpression of lnc-MUC20-9 in 5637 and T24 cells resulted in decreased tumor cell viability and cell clones, decreased migration and invasion, and increased apoptosis. Similarly, nude mice bearing lnc-MUC20-9 overexpressing tumor cells exhibited smaller tumor size and volume than that of mice bearing control cells. Mass spectrometry analysis showed that lnc-MUC20-9 binds to ROCK1, an oncogene whose expression was decreased in lnc-MUC20-9 overexpressing cells. The study revealed that lnc-MUC20-9 has the function of inhibiting tumor growth, migration, and invasion. In BC cells, lnc-MUC20-9 binds to ROCK1 and may be involved in lnc-MUC20-9-mediated tumor suppressor function, which might be potential therapeutic targets for BC.

• Authors: Ranran Dai, You Zhou, Zhishan Chen, Zihao Zou, Zhaojun Pan, Ping Liu, Xingcheng Gao
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 121 Issue 10 Pg. 4214-4225 (10 2020) ISSN: 1097-4644 [Electronic] United States
• PMID: 31898364 (Publication Type: Journal Article)
• Copyright: © 2020 Wiley Periodicals, Inc.

Chemical References

• MUC20 protein, human
• Mucins
• RNA, Long Noncoding
• ROCK1 protein, human
• rho-Associated Kinases

Topics

• Animals
• Apoptosis (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• Genes, Tumor Suppressor
• Humans
• Male
• Mice
• Mice, Nude
• Mucins (genetics, metabolism)
• Neoplasm Invasiveness (genetics)
• RNA, Long Noncoding (genetics, metabolism)
• Transfection
• Tumor Burden (genetics)
• Up-Regulation
• Urinary Bladder Neoplasms (genetics, metabolism, pathology)
• Xenograft Model Antitumor Assays
• rho-Associated Kinases (metabolism)