Tongtong Hao1, Zhenghua Wang2, Jinhui Yang1, Yi Zhang1, Yafeng Shang1, Jiantao Sun3. 1. Department of Urology Surgery, Luoyang Central Hospital Affiliated To Zhengzhou University, Luoyang, China. 2. Department of Laboratory Medicine, Luoyang Central Hospital Affiliated To Zhengzhou University, Luoyang, China. 3. Department of Urology Surgery, Luoyang Central Hospital Affiliated To Zhengzhou University, Luoyang, China. Electronic address: yayalot@sina.com.
Abstract
BACKGROUND: Prostate cancer (PCa) is the second most common cancer among men globally. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to be implicated in tumorigenesis and progression of PCa. However, the pathogenesis of MALAT1 in PCa has not been thoroughly elaborated. METHODS: RT-qPCR assay was conducted to measure expression of MALAT1, microRNA-140 (miR-140) and Baculoviral IAP repeat containing 6 (BIRC6) mRNA. Protein expression of BIRC6 was detected by western blot assay. Cell proliferative ability was assessed by MTS and Edu retention assays. Cell migratory and invasive abilities were evaluated by wound healing assay and Transwell invasion assay, respectively. Cell apoptotic rate was examined using a flow cytometry. The interaction between miR-140 and MALAT1 or BIRC6 3'UTR was explored by luciferase, RNA immunoprecipitation (RIP) and RNA pull down assays. Xenograft models of PCa were established to further explore the role and molecular mechanism of MALAT in PCa tumorigenesis in vivo. RESULTS: MALAT1 and BIRC6 were highly expressed in human PCa tumor tissues and cell lines. MALAT1 or BIRC6 knockdown inhibited cell proliferation, migration and invasion and induced cell apoptosis in PCa. MiR-140 could directly bind with MALAT1 or BIRC6 3'UTR. Moreover, MALAT1 knockdown inhibited BIRC mRNA and protein expression through upregulating miR-140 in PCa cells. Additionally, MALAT1 knockdown inhibited PCa xenograft tumor growth by regulating miR-140/BIRC6 axis in vivo. CONCLUSION: MALAT1 knockdown hindered PCa progression by regulating miR-140/BIRC6 axis in vitro and in vivo, hinting the potential value of MALAT1 in the management of PCa.
BACKGROUND:Prostate cancer (PCa) is the second most common cancer among men globally. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to be implicated in tumorigenesis and progression of PCa. However, the pathogenesis of MALAT1 in PCa has not been thoroughly elaborated. METHODS: RT-qPCR assay was conducted to measure expression of MALAT1, microRNA-140 (miR-140) and Baculoviral IAP repeat containing 6 (BIRC6) mRNA. Protein expression of BIRC6 was detected by western blot assay. Cell proliferative ability was assessed by MTS and Edu retention assays. Cell migratory and invasive abilities were evaluated by wound healing assay and Transwell invasion assay, respectively. Cell apoptotic rate was examined using a flow cytometry. The interaction between miR-140 and MALAT1 or BIRC6 3'UTR was explored by luciferase, RNA immunoprecipitation (RIP) and RNA pull down assays. Xenograft models of PCa were established to further explore the role and molecular mechanism of MALAT in PCa tumorigenesis in vivo. RESULTS:MALAT1 and BIRC6 were highly expressed in humanPCa tumor tissues and cell lines. MALAT1 or BIRC6 knockdown inhibited cell proliferation, migration and invasion and induced cell apoptosis in PCa. MiR-140 could directly bind with MALAT1 or BIRC6 3'UTR. Moreover, MALAT1 knockdown inhibited BIRC mRNA and protein expression through upregulating miR-140 in PCa cells. Additionally, MALAT1 knockdown inhibited PCa xenograft tumor growth by regulating miR-140/BIRC6 axis in vivo. CONCLUSION:MALAT1 knockdown hindered PCa progression by regulating miR-140/BIRC6 axis in vitro and in vivo, hinting the potential value of MALAT1 in the management of PCa.
Authors: Carmela Ferri; Anna Di Biase; Michele Caraglia; Tarik Regad; Vincenzo Desiderio; Marco Bocchetti; Silvia Zappavigna; Sarah Wagner; Pauline Le Vu; Amalia Luce; Alessia Maria Cossu; Jayakumar Vadakekolathu; Amanda Miles; David J Boocock; Alex Robinson; Melanie Schwerdtfeger; Virginia Tirino; Federica Papaccio Journal: J Exp Clin Cancer Res Date: 2022-01-11