LncRNA GAS5 inhibits proliferation and progression of prostate cancer by targeting miR-103 through AKT/mTOR signaling pathway

Xue, Dong; Zhou, Cuixing; Lü, Hao; Xu, Ran; Xu, Xianlin; He, Xiaozhou

doi:10.1007/s13277-016-5429-8

Cited by 95 publications

(88 citation statements)

References 37 publications

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“…Autophagy is recognized as a highly conserved bulk protein degradation pathway that accounts for the turnover of long-lived proteins, disposal of injured organelles. 28 Here, blocking mTOR by its antagonist rapamycin engenders not only mTOR inactivation but also the reactivation of autophagy, indicating that GAS5 may blunt cisplatin-triggered autophagy activation in a mTOR-dependent manner. Though abundant research has been made, the role of autophagy during chemoresistance is blurry and even contradictory.…”

Section: Gas5 Mutes Cisplatin-activated Autophagy In a Mtor-dependementioning

confidence: 90%

Long noncoding RNA growth arrest‐specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR‐dependent manner

Huo

Chen

2018

J of Cellular Biochemistry

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Malignant glioma is a severe type of brain tumor with a grim prognosis. The occurrence of resistance compromises the efficacy of chemotherapy for glioma. Long noncoding RNA growth arrest‐specific 5 (GAS5) has recently become an attractive target for cancer therapy by regulating cell growth, invasion, and migration. Nevertheless, its role in glioma chemoresistance remains elusive. In the current study, the expression of GAS5 was decreased in glioma cell lines, and lower levels of GAS5 were observed in U138 and LN18 glioma cells that had low sensitivity to cisplatin. Functional assay confirmed that knockdown of GAS5 enhanced cell resistance to cisplatin in U87 cells, which had a relatively high expression of GAS5. Conversely, elevation of GAS5 increased cell sensitivity to cisplatin in U138 cells that had a relatively low expression of GAS5. Mechanistically, cisplatin exposure evoked excessive autophagy concomitant with an increase in autophagy‐related LC3II expression and a decrease in autophagy substrate p62 expression, which was reversely muted after GAS5 overexpression. In addition, GAS5 restored cisplatin‐inhibited mammalian target of rapamycin (mTOR) activation. Preconditioning with mTOR antagonist rapamycin engendered not only mTOR inhibition but also abrogated GAS5‐mediated depression in cisplatin‐evoked autophagy. Notably, blocking the mTOR pathway also attenuated GAS5‐increased sensitivity to cisplatin in U138 cells. Cumulatively, these findings indicate that GAS5 may blunt the resistance of glioma cells to cisplatin by suppressing excessive autophagy through the activation of mTOR signaling, implying a promising therapeutic strategy against chemoresistance in glioma.

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Section: Gas5 Mutes Cisplatin-activated Autophagy In a Mtor-dependementioning

confidence: 90%

Long noncoding RNA growth arrest‐specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR‐dependent manner

Huo

Chen

2018

J of Cellular Biochemistry

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“…PCA3 is relieved sponging of miR‐1261, further led to suppression of the target gene PRKD3 , and thus inhibited cell proliferation of PCa . There were studies revealed that an up‐regulated lncRNA GAS5 inhibited the pathogenesis and progression of PCa through directly targeting miR‐103, and negatively mediated the AKT/mTOR signalling pathway . In addition, published research reported that MEG3 inhibited the progression of gastric cancer through regulating miR‐181 family and its downstream targeting molecule Bcl‐2 .…”

Section: Discussionmentioning

confidence: 99%

LncRNA MEG3 inhibits the progression of prostate cancer by modulating miR‐9‐5p/QKI‐5 axis

Huang

Chen

et al. 2018

J Cellular Molecular Medi

136

102

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This study was designed to detecting the influences of lncRNA MEG3 in prostate cancer. Aberrant lncRNAs expression profiles of prostate cancer were screened by microarray analysis. The qRT‐PCR and Western blot were employed to investigating the expression levels of lncRNA MEG3, miR‐9‐5p and QKI‐5. The luciferase reporter assay was utilized to testifying the interactions relationship among these molecules. Applying CCK‐8 assay, wound healing assay, transwell assay and flow cytometry in turn, the cell proliferation, migration and invasion abilities as well as apoptosis were measured respectively. LncRNA MEG3 was a down‐regulated lncRNA in prostate cancer tissues and cells and could inhibit the expression of miR‐9‐5p, whereas miR‐9‐5p down‐regulated QKI‐5 expression. Overexpressed MEG3 and QKI‐5 could decrease the abilities of proliferation, migration and invasion in prostate cancer cells effectively and increased the apoptosis rate. On the contrary, miR‐9‐5p mimics presented an opposite tendency in prostate cancer cells. Furthermore, MEG3 inhibited tumour growth and up‐regulated expression of QKI‐5 in vivo. LncRNA MEG3 was a down‐regulated lncRNA in prostate cancer and impacted the abilities of cell proliferation, migration and invasion, and cell apoptosis rate, this regulation relied on regulating miR‐9‐5p and its targeting gene QKI‐5.

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“…Moreover, overexpression of GAS5 decreased Akt signalling [237,465]. Therefore, lncRNA regulation of Akt signalling seems to highly important in determining the sensitivity of NSCLC cells to the EGFR-TKI gefitinib.…”

Section: Lncrnas Emt and Drug Resistancementioning

confidence: 99%

Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells

Heery

Finn

Cuffe

et al. 2017

Cancers

163

140

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Epithelial mesenchymal transition (EMT), the adoption by epithelial cells of a mesenchymal-like phenotype, is a process co-opted by carcinoma cells in order to initiate invasion and metastasis. In addition, it is becoming clear that is instrumental to both the development of drug resistance by tumour cells and in the generation and maintenance of cancer stem cells. EMT is thus a pivotal process during tumour progression and poses a major barrier to the successful treatment of cancer. Non-coding RNAs (ncRNA) often utilize epigenetic programs to regulate both gene expression and chromatin structure. One type of ncRNA, called long non-coding RNAs (lncRNAs), has become increasingly recognized as being both highly dysregulated in cancer and to play a variety of different roles in tumourigenesis. Indeed, over the last few years, lncRNAs have rapidly emerged as key regulators of EMT in cancer. In this review, we discuss the lncRNAs that have been associated with the EMT process in cancer and the variety of molecular mechanisms and signalling pathways through which they regulate EMT, and finally discuss how these EMT-regulating lncRNAs impact on both anti-cancer drug resistance and the cancer stem cell phenotype.

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LncRNA GAS5 inhibits proliferation and progression of prostate cancer by targeting miR-103 through AKT/mTOR signaling pathway

Cited by 95 publications

References 37 publications

Long noncoding RNA growth arrest‐specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR‐dependent manner

Long noncoding RNA growth arrest‐specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR‐dependent manner

LncRNA MEG3 inhibits the progression of prostate cancer by modulating miR‐9‐5p/QKI‐5 axis

Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells

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