Downregulation of the long noncoding RNA GAS5-AS1 contributes to tumor metastasis in non-small cell lung cancer

Wu, Ying; Lyu, Hui; Liu, Hongbing; Shi, Xuefei; Song, Yong; Liu, Bolin

doi:10.1038/srep31093

Cited by 105 publications

(64 citation statements)

References 48 publications

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“…BRAF-activated lncRNA contributed to cell proliferation and apoptosis by activating autophagy in papillary thyroid carcinoma [28]. Accumulating evidences demonstrated that lncRNA growth arrest-specific 5 (GAS5) acted as a powerful regulator of various biological activities, including tumor metastasis [29], vascular remodeling [30], autoimmune and inflammatory diseases [31]. Recently, GAS5 has been reported to involve in autophagy in NSCLC cells [32], and negatively correlated with mTOR [33,34], which is a crucial regulator of autophagy [35].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of Long Non-Coding RNA GAS5 Increases miR-23a by Targeting ATG3 Involved in Autophagy and Cell Viability

Huang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Autophagy is a process of evolutionarily conservative degradation, which could maintain cellular homeostasis and cope with various types of stress. LncRNAs are considered as competing endogenous RNAs (ceRNAs) contributing to autophagy. GAS5 has been suggested as a new potential factor to mediate autophagy pathway and the underlying mechanism remains to be further confirmed. This study was taken to identify the effect of GAS5/miR-23a/ATG3 axis on autophagy and cell viability. Methods: The western blotting assay was used to detecte the protein levels of LC3, mTOR, Beclin-1, ATG3, ATG5-ATG12 complex and p62. The mRNA level of Pre-miR-23a, Pri-miR-23a, miR-23a, GAS5, LC3, mTOR and ATG3 were quantified by real-time RT-PCR. Dual-luciferase reporter assays were performed to confirm the direct binding of miR-23a and ATG3 or GAS5. Cell viability was evaluated by CCK-8 and flow cytometry. Results: We showed that miR-23a could directly suppress ATG3 expression in 293T cells, which suggested that ATG3 was identified as a target of miR-23a. MiR-23a mimics could restrain LC3 II, Beclin1 levles and ATG5-ATG12 complex formation. Meanwhile, miR-23a also increased the expression of mTOR and p62. Notably, there was a putative miR-23a-binding site in GAS5. MiR-23a overexpression might suppress the GAS5 expression, but the repressive effect was abolished by mutation of binding sites. Importantly, overexpression of GAS5 could inhibit the mature miR-23a and has no effect on miR-23a precursors. Knockdown of GAS5 suppressed the expression of LC3 II, ATG3 and ATG5-ATG12 complex formation, whereas p62 and mTOR levels were promoted. The further results showed that miR-23a overexpression and GAS5 inhibition both significantly suppressed cell viability and promoted the apoptosis rate following LPS stimulation, and knockdown of miR-23a exhibited the opposite effects. Conclusions: Our study revealed that down-regulation GAS5 attenuated cell viability and inhibited autophagy through ATG3-dependent autophagy by regulating miR-23a expression. The results suggested that GAS5/miR-23a/ATG3 axis might be a novel regulatory network contributing to a better understanding of regulation on autophagy program and cell viability.

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Section: Introductionmentioning

confidence: 99%

Knockdown of Long Non-Coding RNA GAS5 Increases miR-23a by Targeting ATG3 Involved in Autophagy and Cell Viability

Huang

et al. 2018

Cell Physiol Biochem

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“…The reduced GAS5-AS1 was significantly correlated with larger tumor, higher TNM stage, and lymph node metastasis for non-small cell lung cancer patients [24]. TTTY14 was significantly correlated with overall survival for GC patients and the prognostic value of TTTY14 was independent to other clinical features [25].…”

Section: Discussionmentioning

confidence: 87%

Integrated analysis reveals potential long non-coding RNA biomarkers and their potential biological functions for disease free survival in gastric cancer patients

et al. 2019

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Background Increasing evidences supported the association between long non-coding RNA (lncRNA) and disease free survival in gastric cancer (GC) patients. The purpose of the current study was to construct and verify a noninvasive preoperative predictive tool for disease free survival in GC patients. Methods There were 265 and 300 GC patients in model dataset and validation dataset respectively. The associations between the lncRNA biomarkers and disease free survival were evaluated by univariate and multivariate Cox regression. Results Thirteen lncRNA biomarkers (GAS5-AS1, AL109615.3, KDM7A-DT, AP000866.2, KCNJ2-AS1, LINC00656, LINC01777, AC046185.3, TTTY14, LINC01526, LINC02523, LINC00592, and C5orf66) were identified as prognostic biomarkers with disease free survival. These thirteen lncRNA biomarkers were combined to construct a prognostic signature for disease free survival. The C-indexes of the current predictive signature in model cohort were 0.849 (95% CI 0.803–0.895), 0.859 (95% CI 0.813–0.905) and 0.888 (95% CI 0.842–0.934) for 1-year, 3-year and 5-year disease free survival respectively. Based on thirteen-lncRNA prognostic signature, patients in model cohort could be stratified into high risk group and low risk group with significant different disease free survival rate (hazard ratio [HR] = 7.355, 95% confidence interval [CI] 4.378–12.356). Good reproducibility of thirteen-lncRNA prognostic signature was confirmed in an external validation cohort (GSE62254) with HR 3.919 and 95% CI 2.817–5.453. Further analysis demonstrated that the prognostic significance of thirteen-lncRNA prognostic signature was independent of other clinical characteristics. Conclusions In conclusion, a simple noninvasive prognostic signature was established for preoperative prediction of disease free survival in GC patients. This prognostic signature might predict the individual mortality risk of disease free survival without pathological information and facilitate individual treatment decision-making. Electronic supplementary material The online version of this article (10.1186/s12935-019-0846-6) contains supplementary material, which is available to authorized users.

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“…Clusters 1, 2, and 6 consist of lncRNAs that exhibit decreased expression in the two malignant cell lines compared to the normal‐like cells; these may represent lncRNAs with tumor suppressive functions (Supplemental 1). For example, one lncRNA from cluster 1, GAS5‐AS1 (Wu et al, ), and one lncRNA from cluster 2, TARID (Arab et al, ), have been shown to be downregulated in tumor compared to normal tissue in various cancers. In contrast, clusters 3 and 4 consist of lncRNAs that show increased expression in the two cancer cell lines compared to the normal‐like MCF‐10A; these may represent lncRNAs that are oncogenic.…”

Section: Resultsmentioning

confidence: 99%

“…Clusters 1, 2, and 6 consist of lncRNAs that exhibit decreased expression in the two malignant cell lines compared to the normal-like cells; these may represent lncRNAs with tumor suppressive functions (Supplemental 1). For example, one lncRNA from cluster 1, GAS5-AS1 (Wu et al, 2016), and one lncRNA from cluster 2, TARID (Arab et al, 2014), have been shown to be downregulated in tumor compared to normal tissue in various cancers.…”

Section: Statistical Analysesmentioning

confidence: 99%

Selective expression of long non‐coding RNAs in a breast cancer cell progression model

Tracy

Tye

Page

et al. 2017

Journal Cellular Physiology

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Long non-coding RNAs (lncRNAs) are acknowledged as regulators of cancer biology and pathology. Our goal was to perform a stringent profiling of breast cancer cell lines that represent disease progression. We used the MCF-10 series, which includes the normal-like MCF-10A, HRAS-transformed MCF-10AT1 (pre-malignant), and MCF-10CA1a (malignant) cells, to perform transcriptome wide sequencing. From these data, we have identified 346 lncRNAs with dysregulated expression across the progression series. By comparing lncRNAs from these datasets to those from an additional set of cell lines that represent different disease stages and subtypes, MCF-7 (early stage, luminal), and MDA-MB-231 (late stage, basal), 61 lncRNAs that are associated with breast cancer progression were identified. Querying breast cancer patient data from The Cancer Genome Atlas, we selected a lncRNA, IGF-like family member 2 antisense RNA 1 (IGFL2-AS1), of potential clinical relevance for functional characterization. Among the 61 lncRNAs, IGFL2-AS1 was the most significantly decreased. Our results indicate that this lncRNA plays a role in downregulating its nearest neighbor, IGFL1, and affects migration of breast cancer cells. Furthermore, the lncRNAs we identified provide a valuable resource to mechanistically and clinically understand the contribution of lncRNAs in breast cancer progression.

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Downregulation of the long noncoding RNA GAS5-AS1 contributes to tumor metastasis in non-small cell lung cancer

Cited by 105 publications

References 48 publications

Knockdown of Long Non-Coding RNA GAS5 Increases miR-23a by Targeting ATG3 Involved in Autophagy and Cell Viability

Knockdown of Long Non-Coding RNA GAS5 Increases miR-23a by Targeting ATG3 Involved in Autophagy and Cell Viability

Integrated analysis reveals potential long non-coding RNA biomarkers and their potential biological functions for disease free survival in gastric cancer patients

Selective expression of long non‐coding RNAs in a breast cancer cell progression model

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