title: Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer.
abstract: Recent studies have highlighted the role of long non-coding RNAs (lncRNAs) in carcinogenesis and have suggested that genes of this class might be used as biomarkers in cancer. However, whether lncRNAs are involved in serous ovarian cancer (SOC) remains largely unknown. In the present study, we focused on lncRNA antisense non-coding RNA in the INK4 locus (ANRIL) and investigated its expression pattern, clinical significance, and biological function in SOC. We found that ANRIL levels were elevated in SOC tissues compared with normal controls and were highly correlated with advanced FIGO stage, high histological grade, lymph node metastasis, and poor prognosis. Multivariate analysis further revealed that ANRIL is an independent prognostic factor for predicting overall survival of SOC patients. In vitro, we compared differential ANRIL levels between SOC parental cell lines (SK-OV-3, HO8910) and highly metastatic sublines (SK-OV-3.ip1, HO8910-PM). Notably, ANRIL was highly expressed in both SK-OV-3.ip1 cells and HO8910-PM cells. SiRNA-mediated ANRIL silencing in these cells impaired cell migration and invasion. Based on the metastasis-related mRNA microarray analysis and subsequent western blotting confirmation, we found that MET and MMP3 are key downstream genes of ANRIL involved in SOC cell migration/invasion. Together, our data suggest that lncRNA ANRIL plays an important role in SOC invasion/metastasis and could represent a novel biomarker for predicting poor survival as well a promising therapeutic target.
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China.
authors.forename: Jun-Jun
authors.initials: JJ
authors.lastname: Qiu
authors.affiliation: Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai 200127, P.R. China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Lin
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China.
authors.forename: Jing-Xin
authors.initials: JX
authors.lastname: Ding
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Feng
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Jin
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China.
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Hua
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement; D018293:Cystadenoma, Serous / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D016019:Survival Analysis
chemical_list: C561518:CDKN2B antisense RNA, human; D062085:RNA, Long Noncoding