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MALAT1 silencing suppresses prostate cancer progression by upregulating miR-1 and downregulating KRAS

Authors Chang J, Xu W, Du X, Hou J

Received 30 January 2018

Accepted for publication 19 April 2018

Published 15 June 2018 Volume 2018:11 Pages 3461—3473


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Tohru Yamada

Junkai Chang, Weibo Xu, Xinyi Du, Junqing Hou

Department of Urology, Huaihe Hospital of Henan University, Kaifeng 475000, China

Background: Prostate cancer (PC) is the second leading cause of cancer-related deaths among men. Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) performed as an oncogene in multiple cancers including PC. However, the molecular mechanisms of MALAT1 implicated in PC progression have not been thoroughly elaborated.
Materials and methods: Reverse transcription-quantitative polymerase chain reaction assay was used to detect the expressions of MALAT1 and microRNA-1 (miR-1). Protein levels of cleaved poly (ADP-ribose) polymerase, cleaved caspase-3, BAX, bcl-2, and KRAS were determined using a western blot assay. Cell proliferation was assessed by colony formation and MTS assays. Cell migration capacity was examined by transwell migration assay (Corning Incorporated, Corning, NY, USA). Apoptosis rate was measured by flow cytometry via double staining of annexin V-FITC and propidium iodide. Luciferase and RNA immunoprecipitation assays were employed to explore the relationship among miR-1, MALAT1, and KRAS.
Results: MALAT1 expression was upregulated and miR-1 expression was downregulated in PC tissues and cell lines. MALAT1 knockdown inhibited cell proliferation and migration, and promoted cell apoptosis in androgen receptor-negative DU145 and PC3 cells. Molecular mechanism explorations disclosed that MALAT1 acted as a molecular sponge of miR-1 in DU145 cells. Moreover, miR-1 downregulation partly abrogated MALAT1 silencing-mediated anti-proliferative, antimigratory, and proapoptotic effects in DU145 and PC3 cells. Further investigation revealed that KRAS was a target of miR-1 in DU145 cells. MALAT1 acted as a competing endogenous RNA of miR-1, resulting in the increase of KRAS expression in DU145 and PC3 cells. Furthermore, miR-1 overexpression hampered proliferation and migration and promoted apoptosis in DU145 and PC3 cells, while these effects were markedly weakened following KRAS upregulation.
Conclusion: MALAT1 knockdown inhibited proliferation and migration and facilitated apoptosis by upregulating miR-1 and downregulating KRAS in androgen receptor-negative PCa cells, providing a new insight into the molecular basis of MALAT1 and a potential biomarker or therapeutic target for suppressing castration-resistant PC.

Keywords: prostate cancer, MALAT1, microRNA-1, KRAS

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