title: Fenofibrate inhibited pancreatic cancer cells proliferation via activation of p53 mediated by upregulation of LncRNA MEG3.
abstract: There is still no suitable drug for pancreatic cancer treatment, which is one of the most aggressive human tumors. Maternally expressed gene 3 (MEG3), a LncRNA, has been suggested as a tumor suppressor in a range of human tumors. Studies found fenofibrate exerted anti-tumor roles in various human cancer cell lines. However, its role in pancreatic cancer remains unknown. The present study aimed to explore the impacts of fenofibrate on pancreatic cancer cell lines, and to investigate MEG3 role in its anti-tumor mechanisms. We used MTT assay to determine cells proliferation, genome-wide LncRNA microarray analysis to identify differently expressed LncRNAs, siRNA or pCDNA-MEG3 transfection to interfere or upregulate MEG3 expression, western blot to detect protein levels, real-time PCR to determine MEG3 level. Fenofibrate significantly inhibited proliferation of pancreatic cancer cells, increased MEG3 expression and p53 levels. Moreover, knockdown of MEG3 attenuated cytotoxicity induced by fenofibrate. Furthermore, overexpression of MEG3 induced cells death and increased p53 expression. Our results indicated fenofibrate inhibited pancreatic cancer cells proliferation via activation of p53 mediated by upregulation of MEG3.
authors: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China.
authors: Duanmin
authors: D
authors: Hu
authors: Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China.
authors: Cunjin
authors: C
authors: Su
authors: Department of Breast Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China.
authors: Min
authors: M
authors: Jiang
authors: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China.
authors: Yating
authors: Y
authors: Shen
authors: Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China.
authors: Aiming
authors: A
authors: Shi
authors: Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China.
authors: Fenglun
authors: F
authors: Zhao
authors: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China.
authors: Ruidong
authors: R
authors: Chen
authors: Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China.
authors: Zhu
authors: Z
authors: Shen
authors: Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China. Electronic address: baojjsdfey@sina.com.
authors: Junjie
authors: J
authors: Bao
authors: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China. Electronic address: sztangwen@163.com.
authors: Wen
authors: W
authors: Tang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D011345:Fenofibrate / Q000008:administration & dosage*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000378:metabolism*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C498907:MEG3 non-coding RNA, human; D062085:RNA, Long Noncoding; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D011345:Fenofibrate
keywords: Fenofibrate; Long non-coding RNAs; MEG3; Microarray analysis; Pancreatic cancer; p53