Circular RNA Circ_0006282 Promotes Cell Proliferation and Metastasis in Gastric Cancer by Regulating MicroRNA-144-5p/Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein β Axis

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2021 Feb 4

PMID 33536789

Citations 7

Authors

Yunqi Hua

Hailong Wang

Haizhen Wang

Xiangming Wu

Li Yang

Chenlin Wang

Xi Li

Yunjian Jin

Min Li

Lina Wang

Changcheng Dong

Fangrui Yin

Affiliations

Soon will be listed here.

Abstract

Background: Circular RNAs (circRNAs) are a class of non-coding RNAs which function as novel regulators in human cancers. In this study, we aimed to investigate the functional roles and related molecular mechanisms of circ_0006282 in gastric cancer (GC) progression.

Methods: Fifty-five GC patients were enrolled in this study. GC cells (AGS and HGC-27) and normal cells (GES-1) were cultured in RPMI1640 added with 10% FBS and 1% penicillin-streptomycin. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to determine the expression levels of circ_0006282, transcription elongation factor B subunit 1 (TCEB1) mRNA, miR-144-5p and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein β (YWHAB; also known as 14-3-3β). RNase R assay was used to determine the characteristic of circ_0006282. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were employed for cell proliferation. Transwell assay was conducted for cell migration and invasion. Western blot assay was carried out to measure the protein levels of Cyclin D1, matrix metalloprotein 9 (MMP9) and YWHAB. Dual-luciferase reporter assay, RNA pull-down assay and RIP assay were adopted to analyze the interaction between miR-144-5p and circ_0006282 or YWHAB. Murine xenograft model assay was performed to explore the function of circ_0006282 in vivo.

Results: Circ_0006282 level was increased in GC tissues and cells compared to normal tissues and cells. Silencing of circ_0006282 restrained GC cell proliferation, migration and invasion. For mechanism analysis, circ_0006282 was identified to function as the sponge for miR-144-5p to positively regulate YWHAB expression in GC cells. Moreover, miR-144-5p inhibition or YWHAB overexpression effectively reversed the impacts of circ_0006282 knockdown on GC cell growth and motility. Additionally, circ_0006282 knockdown blocked tumor growth of GC in vivo.

Conclusion: Circ_0006282 facilitated the malignant behaviors of GC cells through circ_0006282/miR-144-5p/YWHAB axis.

Citing Articles

A Prospective Tumour Marker for Breast Cancer: YWHAB and Its Role in Promoting Oncogenic Phenotypes.

Gopaul V, Winstone L, Gatien B, Nault B, Maiti S, Opperman R Breast Cancer (Dove Med Press). 2024; 16:935-956.

PMID: 39703345 PMC: 11656333. DOI: 10.2147/BCTT.S479384.

YWHAB is regulated by IRX5 and inhibits the migration and invasion of breast cancer cells.

Geng X, Yuan J, Xu W, Zou D, Sun Y, Li J Oncol Lett. 2024; 28(4):469.

PMID: 39119237 PMC: 11306988. DOI: 10.3892/ol.2024.14602.

CircUBA2 promotes the cancer stem cell-like properties of gastric cancer through upregulating STC1 via sponging miR-144-5p.

Wang J, Lin T, Fan D, Gao Y, Chen Y, Wu Y Cancer Cell Int. 2024; 24(1):276.

PMID: 39103836 PMC: 11302268. DOI: 10.1186/s12935-024-03423-0.

YWHAB knockdown inhibits cell proliferation whilst promoting cell cycle arrest and apoptosis in colon cancer cells through PIK3R2.

Zhou X, Chen A, Zhang T Exp Ther Med. 2023; 25(5):193.

PMID: 37090079 PMC: 10119628. DOI: 10.3892/etm.2023.11892.

CircMGA Depresses Myoblast Proliferation and Promotes Myotube Formation through miR-144-5p/FAP Signal.

Wang Z, Zhang M, Li K, Chen Y, Cai D, Chen B Animals (Basel). 2022; 12(7).

PMID: 35405864 PMC: 8996899. DOI: 10.3390/ani12070873.

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