title: Long Noncoding RNA MALAT1 Promotes Aggressive Pancreatic Cancer Proliferation and Metastasis via the Stimulation of Autophagy.
abstract: Recently, pancreatic ductal adenocarcinoma (PDAC) has emerged as one of the most aggressive malignant tumors with the worst prognosis. Previous studies have demonstrated that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is increased in pancreatic cancer and is identified as a diagnostic biomarker. Nonetheless, the molecular mechanism of elevated MALAT1 levels and tumor aggressiveness remains unknown. In this study, MALAT1 was found to be highly expressed in PDAC tissues, and elevated expression was associated with poorer prognoses. In addition, MALAT1 was positively linearly correlated with the expression of LC3B mRNA. Furthermore, several molecules involved in cellular autophagic flux were modulated following the downregulation of MALAT1, including LC3, P62, and LAMP-2. Mechanistically, we found that MALAT1 interacted with RNA binding protein HuR, and silencing of MALAT1 greatly enhanced the posttranscriptional regulation of TIA-1 and had further effects on inhibiting autophagy. MALAT1 was speculated to regulate tumorigenesis via HuR-TIA-1-mediated autophagic activation. Hence, we investigated the biological properties of MALAT1 in terms of tumor proliferation and metastasis by promoting autophagy in vitro In brief, these data demonstrate that MALAT1 could facilitate the advanced progression of tumors in vivo Our study highlights the new roles of MALAT1 on protumorigenic functioning and anticancer therapy via activating autophagy in pancreatic cancer. Mol Cancer Ther; 15(9); 2232-43. ©2016 AACR.
authors.affiliation: Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Le
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Yong-Wei
authors.initials: YW
authors.lastname: Wang
authors.affiliation: Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Guang-Quan
authors.initials: GQ
authors.lastname: Zhang
authors.affiliation: Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Shang-Ha
authors.initials: SH
authors.lastname: Pan
authors.affiliation: Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ji
authors.affiliation: Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Kong
authors.affiliation: Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
authors.forename: Yue-Hui
authors.initials: YH
authors.lastname: Jia
authors.affiliation: Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Xue-Wei
authors.initials: XW
authors.lastname: Bai
authors.affiliation: Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. sunbei70@tom.com.
authors.forename: Bei
authors.initials: B
authors.lastname: Sun
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D000067780:ELAV-Like Protein 1 / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D039102:Poly(A)-Binding Proteins / Q000235:genetics; D011379:Prognosis; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D000074019:T-Cell Intracellular Antigen-1; D023041:Xenograft Model Antitumor Assays
chemical_list: D000067780:ELAV-Like Protein 1; C557041:MALAT1 long non-coding RNA, human; D039102:Poly(A)-Binding Proteins; D062085:RNA, Long Noncoding; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human