LncRNA GAS5 suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition in oral squamous cell carcinoma by regulating the miR-21/PTEN axis

Zeng, Binghui; Li, Ye; Jiang, Fangfang; Wei, Changbo; Chen, Guanhui; Zhang, Wenliang; Zhao, Wei; Yu, Dongsheng

doi:10.1016/j.yexcr.2018.12.014

Cited by 49 publications

(44 citation statements)

References 38 publications

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“…miR-21 can downregulate the Cdc25A, change the negative regulation of the G1/S phase of the cell cycle, and involve in DNA damage repair G2/M check the 19 point [31]. Numerous researches have shown that LncRNA GAS5 acts as a tumor suppressor in many types of malignancies by regulating the miR-21 [32][33][34][35]. In our research, we found overexpression of GAS5 reduced the resistance of drug and increased the apoptosis of gastric cancer cells.…”

Section: Discussionsupporting

confidence: 49%

The Long Noncoding RNA, Growth Arrest-Specific 5, Suppresses Gastric Cancer by Downregulating miR-21 Expression

Peng

Wang

et al. 2020

Pharmacology

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Background: Gastric cancer has become the second major cause of cancer death. The aim of the present study was to explore the relationship between miR-21 and the long noncoding RNA growth arrest-specific 5 (GAS5) in gastric cancer and the effect on gastric cancer cells. Methods: The expression of miR-21 and GAS5 mRNA was analyzed by quantitative real-time-PCR. Overexpression of GAS5 was used to investigate the biological functions of GAS5 in cells. The cell proliferation was detected by cell counting kit-8 assay and the cell migration and invasion were detected by Transwell. Cell apoptosis was evaluated by Annexin V-FITC/PI staining and apoptosis-related proteins were detected by western blot. The mechanism of GAS5 in vivo was evaluated by the tumorigenesis of nude mice, and dual luciferase reporter was used to determine if miR-21 is a GAS5 target. The inhibition of miR-21 and the simultaneous overexpression of GAS5 and miR-21 were further performed, and the above indicators were detected again. Results: GAS5 was low expression and miR-21 was high expression in gastric cancer tissues and cells. GAS5 overexpression reduced the proliferation, migration, and invasion of gastric cancer cells and increased the apoptosis of gastric cancer cells. The growth rate of GAS5 group slowed down and the volume of tumor decreased. miR-21 is a GAS5 target and GAS5 inhibits the proliferation of gastric cancer cells by targeting miR-21. Conclusion: Our research shown that overexpression of GAS5 can significantly inhibit the proliferation, migration, invasion and tumor formation of gastric cancer cells, and promote the apoptosis of gastric cancer cells, which may be related to the targeting inhibition of miR-21 expression by GAS5.

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Section: Discussionsupporting

confidence: 49%

The Long Noncoding RNA, Growth Arrest-Specific 5, Suppresses Gastric Cancer by Downregulating miR-21 Expression

Peng

Wang

et al. 2020

Pharmacology

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“…lncRNA GAS5 functions as a molecular sponge for miR-532-5p in H9c2 cells. In order to clarify the downstream regulation of lncRNA GAS5, previous studies were assessed, and it was revealed that it is able to function as a competing endogenous (ceRNA) to regulate apoptosis (35,36). To further investigate the regulatory mechanisms of lncRNA GAS5 in MIRI, bioinformatics analysis was used to predict target genes.…”

Section: Resultsmentioning

confidence: 99%

Long non‑coding RNA GAS5 regulates myocardial ischemia‑reperfusion injury through the PI3K/AKT apoptosis pathway by sponging miR‑532‑5p

Han

Xia

et al. 2020

Int J Mol Med

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Long non-coding RNAs (lncRNAs) have been revealed to have a marked effect in cardiovascular diseases, including during cardiac development, cardiac hypertrophy, myocardial fibrosis and myocardial ischemic injury. The mechanism of myocardial ischemia-reperfusion injury (MIRI) is very complicated. Although studies have confirmed that lncRNAs are involved, the specific mechanism remains largely unknown. The lncRNA growth arrest specific 5 (GAS5) is known as a regulator of a number of diseases, including certain cancer types. The present study aimed to investigate the function of lncRNA GAS5 in MIRI. The present study reported that the expression of lncRNA GAS5 in H9c2 cells treated with anoxia and reoxygenation was significantly upregulated compared with the control group (P<0.05). Similarly, the expression of lncRNA GAS5 in myocardial tissue obtained from rats treated with MIRI was significantly upregulated compared with the untreated controls (P<0.05). Silencing of lncRNA GAS5 was able to attenuate myocardial damage, as cell viability increased and the apoptosis rate decreased. classical apoptotic proteins involved in MIRI, including B-cell lymphoma 2, Bcl-2-associated X protein and cleaved caspase-3, also exhibited the same trend. At the same time, when lncRNA GAS5 was silenced, microRNA (miR)-532-5p, which was originally expressed at the stage of injury, was upregulated. The luciferase reporter assay results indicated that the lncRNA GAS5 functioned as a molecular sponge of miR-532-5p. The gain-and loss-of-function analysis of miR-532-5p indicated that it was involved in the regulation of MIRI; the trend of results following its overexpression was also consistent with the trend observed following the silencing of lncRNA GAS5. Notably, the protective effect of lncRNA GAS5 silencing on cells was attenuated by miR-532-5p inhibition. Phosphatase and tensin homolog was revealed to be a key target gene for the function of lncRNA GAS5, and its regulation was achieved via binding to miR-532-5p. In other words, silencing lncRNA GAS5 ultimately promoted the activation of the phosphoinositide-3-kinase (PI3K)/protein kinase B pathway (AKT) to reduce myocardial damage. Therefore, lncRNA GAS5 was able to regulate MIRI through the PI3K/AKT apoptosis pathway by sponging miR-532-5p.

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“…140 On the contrary, inhibition of GAS5 promoted proliferation, migration, invasion and EMT of OSCC cells through the miR-21/ PTEN pathway. 141 In addition, GAS5 acted as a ceRNA, effectively becoming a sink for miR-222-3p, activating PTEN/Akt pathway, to play its tumor-suppressive role in vitro and in vivo in papillary thyroid carcinoma (PTC). 104 Knockdown of GAS5 increased proliferation through increase in cyclin D1, CDK4, and p27 expressions and inhibited apoptosis through an increase in Bcl-2 expression via oxidative status and redox balance signaling regulatory axis and interaction between GAS5 and the G6PD protein in melanoma cells.…”

Section: Molecular Mechanismsmentioning

confidence: 99%

<p>Novel Tumor Suppressor lncRNA Growth Arrest-Specific 5 (GAS5) In Human Cancer</p>

Yu¹,

Hann²

2019

OTT

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Long noncoding RNAs (lncRNAs) play crucial regulatory roles in fundamental biological processes, and deregulations of lncRNAs have been linked to numerous human diseases, especially cancers. Of particular interest in this regard is lncRNA GAS5, which is mainly identified as a tumor suppressor in several cancers. GAS5 was significantly low expressed in multiple cancers and was associated with clinic-pathological characteristics and patient survival, indicating a novel potential diagnostic and prognostic biomarker, and a therapeutic target for cancer. Functionally, GAS5 is involved in cell proliferation, metastasis, invasion, apoptosis, epithelial-mesenchymal transition (EMT), and drug resistance, among others, via multiple molecular mechanisms, such as binding to DNA sequences, forming RNA-DNA triplex complex, triggering or suppressing the expression of genes, binding proteins to form chromatin-modifying complex, which activates or represses gene expression, and acting as miRNA sponge to suppress miRNA expression, leading to regulation of miRNA target genes. This review provides an overview of the current state of knowledge and role of GAS5 in clinical relevance, biological functions and molecular mechanisms underlying the dysregulation of expression and function of GAS5 in cancer. Finally, the potential prospective role as diagnostic and prognostic biomarker and therapeutic target in cancer is discussed.

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LncRNA GAS5 suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition in oral squamous cell carcinoma by regulating the miR-21/PTEN axis

Cited by 49 publications

References 38 publications

The Long Noncoding RNA, Growth Arrest-Specific 5, Suppresses Gastric Cancer by Downregulating miR-21 Expression

The Long Noncoding RNA, Growth Arrest-Specific 5, Suppresses Gastric Cancer by Downregulating miR-21 Expression

Long non‑coding RNA GAS5 regulates myocardial ischemia‑reperfusion injury through the PI3K/AKT apoptosis pathway by sponging miR‑532‑5p

<p>Novel Tumor Suppressor lncRNA Growth Arrest-Specific 5 (GAS5) In Human Cancer</p>

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