The HIF-2α-MALAT1-miR-216b axis regulates multi-drug resistance of hepatocellular carcinoma cells via modulating autophagy

Yuan, Peng; Cao, Wenming; Zang, Quan-Ling; Li, Guixin; Guo, Xingyi; Fan, Jianghe

doi:10.1016/j.bbrc.2016.08.065

Cited by 153 publications

(134 citation statements)

References 23 publications

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“…As for roles of lincRNAs in MM autophagy, there are few studies currently. However, a recent study by Yuan et al indicated that lincRNA MALAT1 inhibition and miR-216b suppressed autophagy of hepatocellular carcinoma cells, [21] and Li et al reported that the inhibition of lncRNA ROR increased the expressions of LC3 and Beclin 1 [22]. These results showed that several kinds of lincRNAs promoted autophagy in cancer cells, which verified our results indirectly.…”

Section: Discussionsupporting

confidence: 82%

Knockdown of Linc00515 Inhibits Multiple Myeloma Autophagy and Chemoresistance by Upregulating miR-140-5p and Downregulating ATG14

Yang

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: The purpose of our experiments was to investigate the targeting relationship of linc00515, miR-140-5p and ATG14 and to explore the roles of linc00515, miR-140-5p and ATG14 in autophagy and chemoresistance of melphalan-resistant multiple myeloma cells. Methods: Plasmids that could interfere with the expression of linc00515 and ATG14 were loaded into myeloma cells, which were cultured with melphalan. MTT assay and flow cytometry analysis were utilized to investigate the effect of linc00515, miR-140-5p and ATG14 on the resistance of myeloma cells. QRT-PCR was used to determine the levels of mRNAs. Western blot was utilized to explore the level of ATG14 and autophagy-related proteins. Dual luciferase assay was utilized to explore the targeting relationship between linc00515, miR-140-5p and ATG14. GFP LC3 fluorescence assay was conducted to study the autophagy of cells. Results: The expression of linc00515 and ATG14 were significantly higher in melphalan-resistant myeloma cells. Knockdown of linc00515 and ATG14 led to decreased autophagy and chemoresistance of melphalan-resistant myeloma cells. The forced expression of miR-140-5p suppressed autophagy and chemoresistance of melphalan-resistant myeloma cells. Conclusion: Linc00515 enhanced autophagy and chemoresistance of melphalan-resistant myeloma by directly inhibiting miR-140-5p, which elevated ATG14 level.

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Section: Discussionsupporting

confidence: 82%

Knockdown of Linc00515 Inhibits Multiple Myeloma Autophagy and Chemoresistance by Upregulating miR-140-5p and Downregulating ATG14

Yang

Zhang

et al. 2018

Cell Physiol Biochem

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“…It has been shown to play an important role in multiple cancers via various mechanisms, such as acting as miRNA sponges, enhancing EMT and stimulating apoptosis or autophagy 12, 17, 18, 19, 20. Recently, MALAT1 has been confirmed to induce chemoresistance to oxaliplatin of colorectal cancer by promoting EZH2 41 and regulate multidrug resistance of hepatocellular carcinoma cells by sponging miR‐216b to modulate the expression of HIF‐2 α that is related to autophagy pathway 42. A previous study has shown that MALAT1 is overexpressed in PCa and is a biomarker of poor prognosis,40 indicting it may be involved in modulating chemoresistance of PCa.…”

Section: Discussionmentioning

confidence: 99%

Retracted: Long noncoding RNA MALAT1 enhances the docetaxel resistance of prostate cancer cells via miR‐145‐5p‐mediated regulation of AKAP12

Dong¹,

Lü²,

Xu³

et al. 2018

J Cellular Molecular Medi

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Our present work was aimed to study on the regulatory role of MALAT1/miR‐145‐5p/AKAP12 axis on docetaxel (DTX) sensitivity of prostate cancer (PCa) cells. The microarray data (GSE33455) to identify differentially expressed lncRNAs and mRNAs in DTX‐resistant PCa cell lines (DU‐145‐DTX and PC‐3‐DTX) was retrieved from the Gene Expression Omnibus (GEO) database. QRT‐PCR analysis was performed to measure MALAT1 expression in DTX‐sensitive and DTX‐resistant tissues/cells. The human DTX‐resistant cell lines DU145‐PTX and PC3‐DTX were established as in vitro cell models, and the expression of MALAT1, miR‐145‐5p and AKAP12 was manipulated in DTX‐sensitive and DTX‐resistant cells. Cell viability was examined using MTT assay and colony formation methods. Cell apoptosis was assessed by TUNEL staining. Cell migration and invasion was determined by scratch test (wound healing) and Transwell assay, respectively. Dual‐luciferase assay was applied to analyse the target relationship between lncRNA MALAT1 and miR‐145‐5p, as well as between miR‐145‐5p and AKAP12. Tumour xenograft study was undertaken to confirm the correlation of MALAT1/miR‐145‐5p/AKAP12 axis and DTX sensitivity of PCa cells in vivo. In this study, we firstly notified that the MALAT1 expression levels were up‐regulated in clinical DTX‐resistant PCa samples. Overexpressed MALAT1 promoted cell proliferation, migration and invasion but decreased cell apoptosis rate of PCa cells in spite of DTX treatment. We identified miR‐145‐5p as a target of MALAT1. MiR‐145‐5p overexpression in PC3‐DTX led to inhibited cell proliferation, migration and invasion as well as reduced chemoresistance to DTX, which was attenuated by MALAT1. Moreover, we determined that AKAP12 was a target of miR‐145‐5p, which significantly induced chemoresistance of PCa cells to DTX. Besides, it was proved that MALAT1 promoted tumour cell proliferation and enhanced DTX‐chemoresistance in vivo. There was an lncRNA MALAT1/miR‐145‐5p/AKAP12 axis involved in DTX resistance of PCa cells and provided a new thought for PCa therapy.

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“…Further experiments suggested that MALAT1 most likely contributed to the regulation of TMZ resistance of glioblastoma cell lines by altering EMT status, specifically ZEB1 expression. A newly published paper established that MALAT1 functioned as a regulator in MDR through the HIF-2α-MALAT1-miR-216b axis via modulating autophagy in hepatocellular carcinoma cells [31], hinting at another possible pathway to influence MDR in cancer cells. However, the precise mechanisms of the role of MALAT1 in MDR should be further clarified.…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA MALAT1 Decreases the Sensitivity of Resistant Glioblastoma Cell Lines to Temozolomide

Li¹,

Yuan²,

Yan³

et al. 2017

Cell Physiol Biochem

103

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Background/Aim: Multidrug resistance (MDR) is largely responsible for the failure of chemotherapy. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript (MALAT1) has been reported to be closely related to tumor biology. In the present study, whether MALAT1 contributes to the resistance of glioblastoma cell lines to temozolomide (TMZ) was investigated. Methods: The glioblastoma cell lines U251 and U87 were exposed to increasing concentrations of TMZ to generate TMZ-resistant colonies (the U251/TMZ and U87/TMZ cell lines). The expression levels of MALAT1 and proteins related to epithelial-mesenchymal transition (EMT) were detected by real-time PCR and western blot, respectively. After the transfection of si-MALAT1 or pcDNA-MALAT1, cell viability, mRNA expression of MDR-associated proteins (MDR1, MRP5 and LRP1), and protein expression of EMT related proteins (ZEB1, Snail and SLUG) were evaluated. Results: The expression of MALAT1 was upregulated in the U251/TMZ and U87/TMZ cell lines compared to that in U251 and U87 cell lines, respectively. The treatment of si-MALAT1 decreased MDR1, MRP5, and LRP1 expression, enhanced cell sensitivity to TMZ, and downregulated ZEB1 protein expression, whereas pcDNA-MALAT1 had the opposite effects. However, the effects of si-MALAT1 on MDR -associated protein expression, cell viability, and EMT status were reversed by the transfection of pcDNA-ZEB1, and the effects of pcDNA-MALAT1 were reversed by the transfection of si-ZEB1. In vivo, MALAT1 overexpression enhanced tumors’ TMZ resistance and upregulated ZEB1 expression. Conclusion: MALAT1 decreased the sensitivity of resistant glioma cell lines to TMZ by regulating ZEB1.

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The HIF-2α-MALAT1-miR-216b axis regulates multi-drug resistance of hepatocellular carcinoma cells via modulating autophagy

Cited by 153 publications

References 23 publications

Knockdown of Linc00515 Inhibits Multiple Myeloma Autophagy and Chemoresistance by Upregulating miR-140-5p and Downregulating ATG14

Knockdown of Linc00515 Inhibits Multiple Myeloma Autophagy and Chemoresistance by Upregulating miR-140-5p and Downregulating ATG14

Retracted: Long noncoding RNA MALAT1 enhances the docetaxel resistance of prostate cancer cells via miR‐145‐5p‐mediated regulation of AKAP12

Long Non-Coding RNA MALAT1 Decreases the Sensitivity of Resistant Glioblastoma Cell Lines to Temozolomide

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