Dataset Information

LncRNA MALAT1 contributes to non-small cell lung cancer progression via modulating miR-200a-3p/programmed death-ligand 1 axis.

ABSTRACT: This study was to investigate the expression correlation between long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1), miR-200a-3p and programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC), and their roles in NSCLC. Real-time polymerase chain reaction (PCR) was performed to detect the expressions of MALAT1, miR-200a-3p and PD-L1 in NSCLC tissues and cells for the correlation analysis. The starBase and Targetscan databases were used to predict the binding sites between MALAT1 and miR-200a-3p, and miR-200a-3p and PD-L1, respectively. The targeting relationship between MALAT1 and miR-200a-3p, and miR-200a-3p and PD-L1 were further verified by real-time PCR and dual luciferase reporter gene assay. Cell proliferation was monitored by CCK8 and colony formation assays. The apoptosis was detected using flow cytometry. Wound healing assay and transwell assay were conducted to determine cell migration and invasion. In this study, we demonstrated that in NSCLC tissues, the expression level of MALAT1 was negatively correlated with that of miR-200a-3p, while positively correlated with PD-L1. Besides, MALAT1 promoted proliferation, mobility, migration, and invasion of NSCLC cells via sponging miR-200a-3p. PD-L1 was validated as a target of miR-200a-3p, and indirectly modulated by MALAT1. In conclusion, LncRNA MALAT1 facilitates the progression of NSCLC by modulating miR-200a-3p/PDL1 axis.

SUBMITTER: Wei S

PROVIDER: S-EPMC6595645 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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LncRNA MALAT1 contributes to non-small cell lung cancer progression via modulating miR-200a-3p/programmed death-ligand 1 axis.

Wei Shuquan S Wang Kangwei K Huang Xiaomei X Zhao Zhuxiang Z Zhao Ziwen Z

International journal of immunopathology and pharmacology 20190101

This study was to investigate the expression correlation between long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1), miR-200a-3p and programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC), and their roles in NSCLC. Real-time polymerase chain reaction (PCR) was performed to detect the expressions of MALAT1, miR-200a-3p and PD-L1 in NSCLC tissues and cells for the correlation analysis. The starBase and Targetscan databases were used to predi ...[more]

PMID: 31240979

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Project description:Long noncoding RNA (lncRNAs) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported in diabetic nephropathy (DN) about its effect on podocyte function and cell heat shock induced by hyperglycemia. However, the biological mechanism of MALAT1 regulating DN fibrosis needs further study. In this study, SD rats were administrated with streptozotocin (STZ) to establish a diabetes model. In vitro, human renal tubular epithelial cells (HK-2 and 293T) were treated with high glucose (HG). Here, we found that MALAT1 was upregulated in renal tissues of diabetic rats and HG-treated cells, and HG treatment promoted cell proliferation and invasion. MALAT1 overexpression aggravated protein levels of collagen I (col I), collagen IV (col IV), fibronectin (FN), and laminin (LN) in HK-2 cells, while MALAT1 knockdown exerted the opposite effect. Moreover, the luciferase reporter gene and pull-down assays demonstrated that MALAT1 interacted with miR-2355-3p. The miR-2355-3p level was downregulated in diabetic rats and HG-treated cells, and MALAT1 overexpression inhibited the miR-2355-3p level. Bioinformatics prediction and luciferase reporter gene assay revealed that interleukin 6 signal transducer (IL6ST) was a target of miR-2355-3p. In addition, miR-2355-3p overexpression attenuated fibrosis-related gene levels in HG-treated cells by inhibiting IL6ST expression and inactivating the recombinant signal transducer and activator of the transcription 3 (STAT3) signaling pathway. Knockdown of miR-2355-3p reversed the inhibitory effect of MALAT1 knockdown on IL6ST, col I, col IV, FN, and LN protein levels in HG-induced cells. Overexpression of MALAT1 aggravated cell damage in HG-induced cells via the miR-2355-3p/IL6ST/STAT3 signaling pathway. Finally, enhanced renal fibrosis and kidney tissue damage were observed in diabetic rats. In conclusion, MALAT1 overexpression may enhance renal fibrosis in diabetic rats and cell damage in HG-induced HK-2 cells via the miR-2355-3p/IL6ST axis, which provides a new perspective of DN treatment.

Project description:IntroductionThe clinical successes seen with anti-programmed cell death protein 1/programmed death-ligand 1 (anti-PD-[L]1) agents have galvanized the field of immuno-oncology. We evaluated the landscape and trends in immunotherapy trials involving the PD-(L)1 axis in intrathoracic tumors.MethodsWe identified clinical trials involving anti-PD-(L)1 agents on the ClinicalTrials.gov registry through November 13, 2020 for NSCLC, SCLC, mesothelioma, and thymic epithelial tumor. Clinical trials were indexed according to monotherapy versus combination approaches, PD-(L)1 agents under investigation, clinical settings, trial start date, and partner drug(s). We assessed redundancy among the clinical trials.ResultsWe found 686 clinical trials investigating anti-PD-(L)1 agents for intrathoracic tumors (540 trials in NSCLC, 96 in SCLC, 38 in mesothelioma, and 12 in thymic epithelial tumor). A total of 23 PD-(L)1 inhibitors are undergoing clinical development. A total of 81% of trials assess combination treatment. The number of clinical trials has been growing exponentially in the past decade. PD-(L)1 blockade was frequently combined with chemotherapy or immunomodulatory therapy. Various strategies are in development to overcome resistance to PD-(L)1 blockade in metastatic NSCLC. PD-(L)1 blockade is also increasingly evaluated in neoadjuvant and adjuvant settings. After the U.S. Food and Drug Administration's approval of an anti-PD-(L)1 agent for a specific indication, 14 trials were launched thereafter, which continued to randomize patients to treatments that were inferior to the best available therapy.ConclusionsThe number of clinical trials investigating anti-PD-(L)1 agents in intrathoracic tumors has experienced a steep increase over the past decade with a notable upward trend for combination trials. To reduce duplicative research efforts and accelerate the development of effective immunotherapeutics, improved coordination among key stakeholders and the adoption of innovative trial designs will be vital.

Dataset Information

LncRNA MALAT1 contributes to non-small cell lung cancer progression via modulating miR-200a-3p/programmed death-ligand 1 axis.

Publications

LncRNA MALAT1 contributes to non-small cell lung cancer progression via modulating miR-200a-3p/programmed death-ligand 1 axis.

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