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

Abstract

BackgroundProstate 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 methodsReverse 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.ResultsMALAT1 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.ConclusionMALAT1 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.

Long Non-Coding RNA (lncRNA) Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) Promotes Cell Proliferation and Migration by Regulating miR-143-3p and MAGE Family Member A9 (MAGEA9) in Oral Squamous Cell Carcinoma

“…A growing body of research suggests that MALAT1 functions as a ceRNA to regulate mRNAs by sponging certain miRNAs. MALAT1 promotes progression of prostate cancer by sponging miR-1 to regulate KRAS expression [ 15 ]. MALAT1 promotes cell proliferation by regulating miR-363-3p/EZH2 in colorectal cancer [ 16 ], and MALAT1 acts as an oncogene to regulate FOXP1 expression through sponging miR-509-5p in multiple myeloma [ 17 ].…”

Overexpression of MicroRNA-1 in Prostate Cancer Cells Modulates the Blood Vessel System of an In Vivo Hen's Egg Test–Chorioallantoic Membrane Model

“…In PC, the expression of miR-1 is down-regulated compared to healthy tissue and continues to decrease during tumor progression (13)(14)(15)(16)(17). At the cellular level, miR-1 possesses anti-oncogenic properties, inhibits proliferation and metastasis, and induces apoptosis (11,(18)(19)(20)(21). A main target in PC cells is the proliferative androgen receptor (22,23).…”

Spatholobus suberectus extract suppresses proliferation and EMT, and promotes apoptosis in palmitic acid induced vascular endothelial cells by inhibiting LncRNA MALAT1 via VEGF signaling pathway

“…Human HUVECs cells (purchased from ATCC, USA) were revived using standard procedure and then cultured in Dulbecco's Modified Eagle's Medium (DMEM) with 10% fetal bovine serum (FBS), 100μg/ml penicillin and streptomycin at 37 o C and 5% CO2. Then, the cells in their log phase were digested with trypsin to make single cell suspension for further experiments which were shared into four parts; Part 1: control (normal) cells (no SS and no palmitic acid treatment) Part 2: diabetes-like cells -600μmol/l palmitic acid was added so as to mimic the diabetes-like cells Part 3: flavone treated diabetes-like cells 1 -600μmol/l palmitic acid and 1.00mg/ml of SS extract were added Part 4: SS treated diabetes-like cells 2 -600μmol/l palmitic acid and 2.00mg/ml of SS extract were added Transfection Adopting the method earlier described [19], each of the cells. types were seeded into 6-well plate and incubated in the DMEM medium until the confluence reached 70%.…”