Negative regulation of lncRNA GAS5 by miR-196a inhibits esophageal squamous cell carcinoma growth

Journal Article · Mon Jan 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.11.119· OSTI ID:23134474

Wang, Kai; Li, Juan ^[1]; Xiong, Gang ^[2]; He, Gang; Guan, Xingying ^[1]; Yang, Kang ^[2]; Bai, Yun ^[1]

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1. Department of Medical Genetics, Department of Basic Medicine, Third Military Medical University, Chongqing 400038 (China)
2. Department of Thoracic and Cardiac Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

Highlights: • lncRNA GAS5 is a novel target of miR-196a. • miR-196a decreased the expression of GAS5 possibly through RISC. • GAS5 expression is significantly decreased in patients with ESCC. • The reduced expression of GAS5 in ESCC may be not related to DNA methylation but the high level of miR-196a. • GAS5 functions as a tumor suppressor gene by inhibiting cell growth. MiR-196a could play important roles in carcinogenesis by targeting many protein coding genes. However, little is known about whether miR-196a can target any long non-coding RNAs (lncRNAs). In the present study, we screen lncRNAs which are regulated by miRNA-196a in human esophageal squamous cell carcinoma (ESCC). We found that miR-196a could suppress the expression of lncRNA growth arrest-specific 5(GAS5). GAS5 is frequently down-regulated in 86 paired human ESCC tissues. Importantly, there was lower GAS5 expression in the late stage of ESCC patients. The reduced expression of GAS5 in ESCC may not be related to DNA methylation but related to the high expression of miR-196a. In vitro and in vivo studies indicated that GAS5 could inhibit the growth of ESCC cells. Using Chromatin Isolation by RNA Purification–qPCR, we found that miR-196a could bind to GAS5. The Luciferase Reporter Assay indicated that miR-196a could bind to the seventh exon of GAS5. Additionally, both GAS5 and miR-196a could bind to Ago2 which is a key component of the RNA-induced silencing complex (RISC). Together, these results suggest that GAS5 functions as a tumor suppressor gene in ESCC and is regulated by miR-196a involved in RISC.

• OSTI ID: 23134474
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 495; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARCINOGENESIS
CARCINOMAS
DNA
ESOPHAGUS
LUCIFERASE
METHYLATION
RNA