title: Overexpression of FAM83H-AS1 indicates poor patient survival and knockdown impairs cell proliferation and invasion via MET/EGFR signaling in lung cancer.
abstract: Whole transcriptome analyses of next generation RNA sequencing (RNA-Seq) data from human cancer samples reveled thousands of uncharacterized non-coding RNAs including long non-coding RNA (lncRNA). Recent studies indicated that lncRNAs are emerging as crucial regulators in cancer processes and potentially useful as biomarkers for cancer diagnosis and prognosis. To delineate dysregulated lncRNAs in lung cancer, we analyzed RNA-Seq data from 461 lung adenocarcinomas (LUAD) and 156 normal lung tissues. FAM83H-AS1, one of the top dysregulated lncRNAs, was found to be overexpressed in tumors relative to normal lung and significantly associated with worse patient survival in LUAD. We verified this diagnostic/prognostic potential in an independent cohort of LUAD by qRT-PCR. Cell proliferation, migration and invasion were decreased after FAM83H-AS1 knockdown using siRNAs in lung cancer cells. Flow cytometry analysis indicated the cell cycle was arrested at the G2 phase after FAM83H-AS1 knockdown. Mechanistically, we found that MET/EGFR signaling was regulated by FAM83H-AS1. Our study indicated that FAM83H-AS1 plays an important role in lung tumor progression and may be potentially used as diagnostic/prognostic marker. Further characterization of this lncRNA may provide a novel therapeutic target impacting MET/EGFR signaling.
authors.affiliation: Xian Jiaotong University, Xi'an, China.|Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Xinjiang Medical University, Urumqi, China.
authors.forename: Shumei
authors.initials: S
authors.lastname: Feng
authors.affiliation: Guangdong Medical University, Zhanjiang, China.
authors.forename: Wenmei
authors.initials: W
authors.lastname: Su
authors.affiliation: Xinjiang Medical University, Urumqi, China.
authors.forename: Shengbin
authors.initials: S
authors.lastname: Bai
authors.affiliation: Xinjiang Medical University, Urumqi, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Guangxi Medical University, Nanning, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of Michigan, USA.
authors.forename: Dafydd G
authors.initials: DG
authors.lastname: Thomas
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Jules
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Rishindra M
authors.initials: RM
authors.lastname: Reddy
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Carrott
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Lynch
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Chang
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Beer
authors.affiliation: Xian Jiaotong University, Xi'an, China.
authors.forename: You-Min
authors.initials: YM
authors.lastname: Guo
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Guoan
authors.initials: G
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D062085:RNA, Long Noncoding; C000602203:onco-lncRNA-3, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met