Downregulation of gas5 increases pancreatic cancer cell proliferation by regulating CDK6

Lü, Xiang; Fang, Yuan; Wang, Zhengting; Xie, Junjie; Zhan, Qimin; Deng, Xiaxing; Chen, Hao; Jin, Jiabin; Peng, Chenghong; Li, Hongwei; Shen, Baiyong

doi:10.1007/s00441-013-1711-x

Cited by 137 publications

(103 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…GAS5 functions as a potential tumor suppressor and is downregulated in several types of cancer (28). GAS5 is also involved in the regulation of mammalian cell apoptosis and cell population growth (31)(32)(33). The downregulation of GAS5 protects T cell lines as well as untransformed human T-lymphocytes (34).…”

Section: Discussionmentioning

confidence: 99%

Association of long non‑coding RNA GAS5 and miR‑21 levels in CD4+ T cells with clinical features of systemic lupus erythematosus

et al. 2017

View full text Add to dashboard Cite

Abstract. The present study aimed to assess the expression of growth arrest-specific 5 (GAS5) and microRNA (miR)-21 in systemic lupus erythematosus (SLE), and attempted to explore their association with clinical features. CD4 + T cells were isolated from peripheral blood of healthy donors and SLE patients by magnetic-activated cell sorting. GAS5 and miR-21 expression levels in cluster of differentiation (CD)4 + T cells were measured by reverse-transcription quantitative polymerase chain reaction. The results revealed that GAS5 and miR-21 levels were significantly elevated in CD4 + T cells of patients with SLE compared with those in control subjects (P<0.05). Regarding clinical features, SLE patients with ulceration had higher GAS5 expression levels in CD4 + T cells than those without ulceration (P<0.05), and the expression of miR-21 was significantly higher in CD4 + T cells of SLE patients with low levels of complement component 3 (C3) than in those with normal levels of complement C3 (P<0.05).In conclusion, GAS5 and miR-21 in CD4 + T cells may serve as potential biomarkers for the diagnosis and monitoring of the progression of SLE. IntroductionSystemic lu pus erythematosus (SLE) is a multisystemic, chronic inflammatory autoimmune disease of unknown etiology. It is characterized by various pathogenic autoantibodies and immune complexes as well as damage to multiple organ systems, and the course of SLE is long followed by remission and acute attack. The prevalence varies from 31-70/100,000 individuals in China and from 20-70/100,000 individuals worldwide. It is sex-associated, occurring nine times more often in women than in men, particularly in women of child-bearing age (15-35 years) (1-3). The interaction between certain genetic and environmental factors, including chemical factors, viruses and drugs, damages normal immune tolerance and contributes to SLE. Dysfunctional T cells interact with new antigens constantly, leading to a persistent autoimmune reaction (4,5). Previous studies have confirmed that the abnormal activation and proliferation of self-reactive cluster of differentiation (CD)4 + T lymphocytes have a central role in SLE. CD4 + T cells interact with antigen-specific B cells, to make the latter ones become more effective and produce autoantibodies. In addition, CD4 + T cells produce various cytokines when they are activated, which may engender inflammatory reactions (6,7).Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNA with transcripts longer than 200 nucleotides. They have numerous important biological functions through different molecular mechanisms, and are closely associated with a variety of clinical diseases, including tumors, metabolic disease and autoimmune diseases. Growth arrest-specific 5 (GAS5), a non-coding gene that hosts a number of small nucleolar RNAs, has been suggested to have numerous important roles in apoptosis and cell growth inhibition. Previous studies have reported that human GAS5 was upregulated in osteoarthritis (OA) patients (8) and downregulated i...

show abstract

Section: Discussionmentioning

confidence: 99%

Association of long non‑coding RNA GAS5 and miR‑21 levels in CD4+ T cells with clinical features of systemic lupus erythematosus

et al. 2017

View full text Add to dashboard Cite

show abstract

“…GAS5 is proven to be associated with the cell cycle and cell progression, and critical to normal growth arrest (26). GAS5 overexpression inhibits cell cycle progression while GAS5 inhibition decreases cell apoptosis and contributes to faster cell cycle progression (27,28).…”

Section: Structural Characterization and Biological Functions Of Gas5mentioning

confidence: 99%

“…Furthermore, cyclin-dependent kinase 6 (CDK6) expression was negatively regulated by GAS5 in vitro and in vivo. Knockdown of CDK6 partially abrogates GAS5-siRNA-induced cancer cell proliferation (28).…”

Section: Gas5 Status In Cancersmentioning

confidence: 99%

“…GAS5 was demonstrated to inhibit tumor cell proliferation in gastric cancer, pancreatic cancer, renal carcinoma cell lines and bladder cancer cells (16,27,28,31).…”

Section: Gas5 Regulates Proliferationmentioning

confidence: 99%

“…In addition, p21 is downregulated or lost in several cancer types with its inhibitory control over the cell cycle (45,46). GAS5 exerts its effect in bladder cancer partly by regulating CDK6, since knockdown of GAS5 increased CDK6 mRNA and protein levels (27,28). CDK6 regulated the cell cycle, and dysregulation of CDK6 is associated with bladder cancer progression (47,48).…”

Section: Molecular Mechanism and Action Of Gas5mentioning

confidence: 99%

See 2 more Smart Citations

Long non-coding RNA growth arrest-specific transcript 5 in tumor biology

2015

Oncology Letters

View full text Add to dashboard Cite

Abstract. The recognition of the biological relevance of long non-coding RNA (lncRNA) molecules has only recently been recognized as one of the most significant advances in contemporary molecular biology. A growing body of evidence indicates that lncRNAs act not only as the intermediary between DNA and protein but also as significant protagonists of cellular functions. The dysregulation of lncRNAs has increasingly been linked to numerous human diseases, particularly cancers. Recent studies have demonstrated that the lncRNA growth arrest-specific transcript 5 (GAS5) was pervasively downexpressed in most human cancers compared with non-cancerous adjacent tissues including gastric, breast, lung and prostate cancer. In addition, patients with decreased GAS5 expression have a significantly poorer prognosis than those with higher expression. Furthermore, GAS5 is involved in the control of cell apoptosis, proliferation, metastasis, angiogenesis, DNA repair and tumor cell metabolism. This review provides an overview of the current knowledge concerning the role of GAS5 in tumor expression and biology function.

show abstract

GAS5 Gene

Aly

Hirose

2016

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Growth arrest‐specific 5 ( GAS5 ) is a nonprotein‐coding small nucleolar ribonucleic acid (snoRNA) host gene. Ten box C/D snoRNAs are encoded within the 11 introns of the human GAS5 gene, whereas the spliced exons have little protein‐coding potential. GAS5 has been classified as a member of the 5′ oligopyrimidine tract (5′ TOP) gene family. Growth‐dependent translation mediated by the 5′ TOP sequence determines the level of the GAS5 spliced transcript ( GAS5 long noncoding RNA (lncRNA)) by a mechanism of translation‐linked RNA degradation. GAS5 lncRNA plays a critical role in arresting cell growth and inducing apoptosis. The decreased expression of GAS5 in multiple cancers suggests that GAS5 acts as a tumour suppressor. GAS5 lncRNA controls the gene expression of critical cell cycle and apoptosis regulators. GAS5 lncRNA suppresses steroid‐responsive transcription by direct association with several steroid receptors and acts as a molecular decoy. GAS5 lncRNA also sequestrates a specific functional microRNA. Key Concepts GAS5 is a nonprotein‐coding small nucleolar RNA host gene. A translation‐linked mRNA decay pathway controls growth arrest‐specific accumulation of GAS5 by way of its 5′‐terminal oligopyrimidine tract (5′ TOP). GAS5 functions to arrest cell growth and induce apoptosis. GAS5 controls expression of genes for critical regulators of the cell cycle and apoptosis. GAS5 binds to steroid hormone receptors through its 3′‐terminal stem‐loop structure to suppress steroid‐responsive transcription. GAS5 sequestrates a specific functional microRNA.

show abstract

Downregulation of gas5 increases pancreatic cancer cell proliferation by regulating CDK6

Cited by 137 publications

References 25 publications

Association of long non‑coding RNA GAS5 and miR‑21 levels in CD4+ T cells with clinical features of systemic lupus erythematosus

Association of long non‑coding RNA GAS5 and miR‑21 levels in CD4+ T cells with clinical features of systemic lupus erythematosus

Long non-coding RNA growth arrest-specific transcript 5 in tumor biology

GAS5 Gene

Contact Info

Product

Resources

About