title: Long non-coding RNA LINC00672 contributes to p53 protein-mediated gene suppression and promotes endometrial cancer chemosensitivity.
abstract: Thousands of long intergenic non-protein coding RNAs (lincRNAs) have been identified in mammals in genome-wide sequencing studies. Some of these RNAs have been consistently conserved during the evolution of species and could presumably function in important biologic processes. Therefore, we measured the levels of 26 highly conserved lincRNAs in a total of 176 pairs of endometrial carcinoma (EC) and surrounding non-tumor tissues of two distinct Chinese populations. Here, we report that a lincRNA,LINC00672, which possesses an ultra-conserved region, is aberrantly down-regulated during the development of EC. Nevertheless,LINC00672is a p53-targeting lincRNA acting along with heterogeneous nuclear ribonucleoproteins as a suppressive cofactor, which locally reinforces p53-mediated suppression ofLASP1, an evolutionarily conserved neighboring gene ofLINC00672and putatively associated with increased tumor aggressiveness, during anti-tumor processes.LINC00672overexpression could lower the levels ofLASP1and slow the development of malignant phenotypes of EC bothin vitroandin vivoMoreover,LINC00672significantly increased the 50% inhibitory concentration of paclitaxel in EC cells and increased the sensitivity of xenograft mice to paclitaxel. These findings indicate thatLINC00672can influenceLASP1expression as a locus-restricted cofactor for p53-mediated gene suppression, thus impacting EC malignancies and chemosensitivity to paclitaxel.
authors.affiliation: From the Department of Genetics, Medical College of Soochow University, Suzhou 215123.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: the Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: the Departments of Radiotherapy and Oncology and.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, and.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: From the Department of Genetics, Medical College of Soochow University, Suzhou 215123.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: From the Department of Genetics, Medical College of Soochow University, Suzhou 215123.
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Deng
authors.affiliation: From the Department of Genetics, Medical College of Soochow University, Suzhou 215123.
authors.forename: Mingxing
authors.initials: M
authors.lastname: An
authors.affiliation: From the Department of Genetics, Medical College of Soochow University, Suzhou 215123.
authors.forename: Siqi
authors.initials: S
authors.lastname: Wu
authors.affiliation: From the Department of Genetics, Medical College of Soochow University, Suzhou 215123.
authors.forename: Rui
authors.initials: R
authors.lastname: Ma
authors.affiliation: the Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
authors.affiliation: From the Department of Genetics, Medical College of Soochow University, Suzhou 215123, zhouyifeng@suda.edu.cn.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D060588:LIM Domain Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000494:pharmacology; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D017239:Paclitaxel
keywords: Lasp1; endometrial cancer; gene regulation; heterogeneous nuclear ribonucleoprotein (hnRNP); long noncoding RNA (long ncRNA, lncRNA); p53; paclitaxel (taxol)