GAS5 knockdown reduces the chemo-sensitivity of non-small cell lung cancer (NSCLC) cell to cisplatin (DDP) through regulating miR-21/PTEN axis

Cao, Lin; Chen, Jia; Ou, Baiqing; Liu, Cuizhong; Zou, Yan; chen, Qiong

doi:10.1016/j.biopha.2017.06.089

Cited by 108 publications

(98 citation statements)

References 39 publications

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“…Cisplatin (DDP) is the first-line drug used to treat NSCLC. However, most patients suffer from DDP resistance, greatly limiting the treatment of NSCLC [2]. Therefore, studies on bioactive agents that circumvent these limitations and target NSCLC are needed.…”

Section: Introductionmentioning

confidence: 99%

Asiatic Acid (AA) Sensitizes Multidrug-Resistant Human Lung Adenocarcinoma A549/DDP Cells to Cisplatin (DDP) via Downregulation of P-Glycoprotein (MDR1) and Its Targets

Cheng¹,

Liao²,

Hu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: P-glycoprotein (P-gp, i.e., MDR1) is associated with the phenotype of multidrug resistance (MDR) and causes chemotherapy failure in the management of cancers. Searching for effective MDR modulators and combining them with anticancer drugs is a promising strategy against MDR. Asiatic acid (AA), a natural triterpene isolated from the plant Centella asiatica, may have an antitumor activity. The present study assessed the reversing effect of AA on MDR and possible molecular mechanisms of AA action in MDR1-overexpressing cisplatin (DDP)-resistant lung cancer cells, A549/DDP. Methods: Human lung adenocarcinoma A549/DDP cells were either exposed to different concentrations of AA or treated with DDP, and their viability was measured by the MTT assay. A Rhodamine 123 efflux assay, immunofluorescent staining, ATPase assay, reverse-transcription PCR (RT-PCR), and western blot analysis were conducted to elucidate the mechanisms of action of AA on MDR. Results: Our results showed that AA significantly enhanced the cytotoxicity of DDP toward A549/DDP cells but not its parental A549 cells. Furthermore, AA strongly inhibited P-gp expression by blocking MDR1 gene transcription and increased the intracellular accumulation of the P-gp substrate Rhodamine 123 in A549/DDP cells. Nuclear factor (NF)-kB (p65) activity, IkB degradation, and NF-kB/p65 nuclear translocation were markedly inhibited by pretreatment with AA. Additionally, AA inhibited the MAPK–ERK pathway, as indicated by decreased phosphorylation of ERK1 and -2, AKT, p38, and JNK, thus resulting in reduced activity of the Y-box binding protein 1 (YB1) via blockage of its nuclear translocation. Conclusions: AA reversed P-gp-mediated MDR by inhibition of P-gp expression. This effect was likely related to downregulation of YB1, and this effect was mediated by the NF-kB and MAPK–ERK pathways. AA may be useful as an MDR reversal agent for combination therapy in clinical trials.

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Section: Introductionmentioning

confidence: 99%

Asiatic Acid (AA) Sensitizes Multidrug-Resistant Human Lung Adenocarcinoma A549/DDP Cells to Cisplatin (DDP) via Downregulation of P-Glycoprotein (MDR1) and Its Targets

Cheng¹,

Liao²,

Hu³

et al. 2018

Cell Physiol Biochem

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“…Second, the same lncRNA‐miRNA‐mRNA axis may modulate diverse biological functions in different diseases. The GAS5‐miR‐21‐PTEN axis suppressed breast cancer cell proliferation and increased the chemo‐sensitivity of nonsmall cell lung cancer cells to cisplatin . The CHRF‐miR‐489‐Myd88 axis was also capable of triggering the development of pulmonary fibrosis .…”

Section: Conclusion and Perspectivementioning

confidence: 99%

The novel regulatory role of lncRNA‐miRNA‐mRNA axis in cardiovascular diseases

Huang

2018

J Cellular Molecular Medi

395

288

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Long noncoding RNAs (lncRNAs) are RNAs longer than 200 nt in length that are characterized by low levels of sequence conservation and expression; lncRNAs modulate various biological functions at epigenetic, transcriptional and post‐transcriptional levels, or directly regulate protein activity. As a family of small and evolutionarily conserved noncoding RNAs, microRNAs (miRNAs) are capable of regulating physiological and pathological processes via inhibiting target mRNA translation or promoting mRNA degradation. A number of studies have confirmed that both lncRNAs and miRNAs are closely associated with the development of cardiovascular diseases (CVDs), such as cardiac remodelling, heart failure, myocardial injury and arrhythmia, and that they act as biomarkers, potential therapeutic targets or strong indicators of prognosis; however, the underlying molecular mechanism has not been elucidated. Recently, emerging evidence showed that the novel regulatory mechanism underlying the crosstalk among lncRNAs, miRNAs and mRNAs plays a pivotal role in the pathophysiological processes of CVDs in response to stress stimuli. In this review, I comprehensively summarized the regulatory relationship of lncRNAs, miRNAs and mRNAs and highlighted the important role of the lncRNA‐miRNA‐mRNA axis in CVDs.

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“…19 For research in glioma, GAS5 exerts an inhibitory effect on cell proliferation and malignancy of human glioma stem cell. 23 Further mechanism analysis conferred that exposure to cisplatin evoked excessive autophagy by increasing the conversion of LC3I to LC3II and suppressing p62 accumulation, both markers to evaluate autophagic flux. 21 In this study, depression of GAS5 reduced the sensitivity of U87 cells that had high GAS5 levels to cisplatin by inhibiting cell viability, colony formation, and promoting cell apoptosis.…”

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

confidence: 99%

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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GAS5 knockdown reduces the chemo-sensitivity of non-small cell lung cancer (NSCLC) cell to cisplatin (DDP) through regulating miR-21/PTEN axis

Cited by 108 publications

References 39 publications

Asiatic Acid (AA) Sensitizes Multidrug-Resistant Human Lung Adenocarcinoma A549/DDP Cells to Cisplatin (DDP) via Downregulation of P-Glycoprotein (MDR1) and Its Targets

Asiatic Acid (AA) Sensitizes Multidrug-Resistant Human Lung Adenocarcinoma A549/DDP Cells to Cisplatin (DDP) via Downregulation of P-Glycoprotein (MDR1) and Its Targets

The novel regulatory role of lncRNA‐miRNA‐mRNA axis in cardiovascular diseases

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

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