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

Abstract

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.

AKAP12 deficiency impairs VEGF‐induced endothelial cell migration and sprouting

“…However, the latter is the more likely given the fact that hypoxia, lipopolysaccharide, and lysophosphatidylcholine are able to induce AKAP12 expression. More recently the long noncoding RNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) was found to regulate the expression of miR‐145‐5p, which in turn targeted AKAP12 . While these findings were made using prostate cancer cells, MALAT1, and miR‐145 are both known to affect endothelial cell migration and angiogenesis, especially in cells exposed to hypoxia and in the tumour microenvironment.…”

miR‐211 sponges lncRNA MALAT1 to suppress tumor growth and progression through inhibiting PHF19 in ovarian carcinoma

“…LncRNAs are emerging as key players in cancer formation and development. MALAT1, also known as nuclearenriched transcript 2, is the most well-known lncRNA that plays an important role in the pathogenesis and progression of different tumors (51)(52)(53)(54)(55)(56). Elevated expression of MALAT1 promotes cell proliferation, invasion, migration, and metastasis in OC.…”

MiR‐145 in cancer therapy resistance and sensitivity: A comprehensive review

“…Targeting EGFR by miR‐145 inhibited cell growth and sensitized NSCLC cells to erlotinib 6 . LncRNA MALAT1 enhanced the docetaxel resistance of prostate cancer cells via miR‐145‐5p‐mediated regulation of AKAP12 22 . MiR‐145 enhanced the sensitivity of NSCLC to gefitinib through targeting ADAM19 5 .…”

“…Researchers are currently attempting to explore the target genes of miR‐145 and their signaling pathways involved in altering therapeutic response, which is significant for the development of miRNA‐related therapies. Strikingly, various research has disclosed that miR‐145 acts in reversion of therapeutic resistance in multiple tumors, including lung cancer, 3‐6 esophageal squamous cell carcinoma (ESCC), 7‐9 ovarian carcinoma, 10,11 glioma, 12,13 hepatocellular carcinoma (HCC), 14‐16 breast cancer, 17 colorectal cancer (CRC) 18‐21 prostate cancer, 22,23 bladder cancer, 24 gastric cancer (GC), 25,26 pancreatic adenocarcinoma 27 and cervical cancer 28,29 …”