title: A novel long non-coding RNA FOXCUT and mRNA FOXC1 pair promote progression and predict poor prognosis in esophageal squamous cell carcinoma.
abstract: Accumulating evidences demonstrated that many long non-coding RNAs (lncRNAs) can cooperate with the adjacent coding genes, forming into "lncRNA-mRNA gene pairs" in multiple biological cellular processes. Here, we showed that a novel long non-coding RNA FOXCUT (FOXC1 promoter upstream transcript) and its neighboring gene FOXC1 played a similar important role in the oncogenesis and progression of esophageal squamous cell carcinoma (ESCC). In this study, the expression of FOXCUT/FOXC1 was measured in 82 ESCC tissues and adjacent noncancerous tissues by real-time quantitative PCR (qPCR). The prognostic significance of the lncRNA-mRNA gene pair was evaluated using Kaplan-Meier survival analysis and log-rank test. Cell biological experiments were performed in ESCC cell lines to explore their functions in tumor progression. Notably elevated FOXCUT and FOXC1 expression levels were observed in cancerous tissues compared to adjacent noncancerous tissues (86.6% and 84.1%, respectively; P < 0.01), showing strong correlations with poor differentiation, advanced lymph node classification and metastasis (P < 0.05). Moreover, patients with upregulated FOXCUT or FOXC1 experienced a significantly worse prognosis than those with downregulated FOXCUT or FOXC1 (P < 0.001 and P = 0.014, respectively). In addition, the expression of FOXCUT was positively correlated with expression of FOXC1 in ESCC specimens. And the expression of FOXC1 was also decreased as the FOXCUT expression was silenced by siRNA. Assays in vitro demonstrated that knockdown of either FOXCUT or FOXC1 remarkably inhibited cell proliferation, colony formation, migration, invasion in ESCC cells. In conclusion, FOXCUT may be functionally involved in the tumor progression and survival of ESCC patients, at least in part, by modulating FOXC1. FOXCUT and FOXC1 may function as a lncRNA-mRNA gene pair, which may represent a potential prognostic biomarker and therapeutic target for ESCC patients.
authors.affiliation: Key Laboratory of Oncology, Cancer Center, Division of Internal Medicine, Chinese PLA General Hospital & Chinese PLA Medical School Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Pan
authors.affiliation: Department of Oncology, The 161th Hospital of PLA Wuhan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yao
authors.affiliation: Key Laboratory of Oncology, Cancer Center, Division of Internal Medicine, Chinese PLA General Hospital & Chinese PLA Medical School Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Nanlou Department of Respiratory Disease, Chinese PLA General Hospital Beijing, China.
authors.forename: Changxi
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Oncology, Cancer Center, Division of Internal Medicine, Chinese PLA General Hospital & Chinese PLA Medical School Beijing, China.
authors.forename: Peiliang
authors.initials: P
authors.lastname: Geng
authors.affiliation: Key Laboratory of Oncology, Cancer Center, Division of Internal Medicine, Chinese PLA General Hospital & Chinese PLA Medical School Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
authors.affiliation: Nanlou Department of Respiratory Disease, Chinese PLA General Hospital Beijing, China.
authors.forename: Xiangqun
authors.initials: X
authors.lastname: Fang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D062085:RNA, Long Noncoding; D012333:RNA, Messenger
keywords: ESCC; FOXC1; FOXCUT; lncRNA; prognosis; progression