Downregulation of LncRNA GAS5 promotes liver cancer proliferation and drug resistance by decreasing PTEN expression
Accumulating evidence has shown that the long noncoding RNAs (lncRNAs) play a crucial role in the regulation of hepatocellular carcinoma (HCC) progression and drug resistance. In this study, we aimed to investigate the biological function roles of lncRNAs growth arrest-specific 5 (GAS5) and its underlying molecular mechanism in the development of HCC. qRT-PCR was used to detect GAS5, miR-21, and PTEN levels. MTT, cell counting assays, and xenograft mouse model were applied to measure cell proliferation rate in vitro and in vivo. The luciferase reporter assay and RNA immune-precipitation assay were introduced to evaluate the relationship between GAS5 and miR-21. We found that GAS5 was downregulated in HCC cell lines and tumor tissues. Knockdown of GAS5 enhanced HCC cell proliferation in vitro and in vivo and increased HCC cell resistance to doxorubicin. GAS5 acted as a sponge for miR-21 silencing and consequently led to the elevation of PTEN expression. Our data demonstrated that GAS5 functioned as a tumor suppressor role in HCC through regulation of miR-21-PTEN singling pathways, suggesting a potential application of GAS5 in HCC therapy.
KeywordsHepatocellular carcinoma GAS5 miR-21 PTEN Tumor suppressor
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
All applicable international, national, and/or institutional guidelines for the care were followed.
Informed consent was derived from all the participants.
- Avgeris M, Tsilimantou A, Levis PK, Tokas T, Sideris DC, Stravodimos K, Ardavanis A, Scorilas A (2018) Loss of GAS5 tumour suppressor lncRNA: an independent molecular cancer biomarker for short-term relapse and progression in bladder cancer patients. Br J Cancer 119(12):1477–1486CrossRefGoogle Scholar
- Yuan SX, Yang F, Yang Y, Tao QF, Zhang J, Huang G, Yang Y, Wang RY, Yang S, Huo XS, Zhang L, Wang F, Sun SH, Zhou WP (2012) Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients’ poor recurrence-free survival after hepatectomy. Hepatology 56(6):2231–2241CrossRefGoogle Scholar