title: Upregulated NNT-AS1, a long noncoding RNA, contributes to proliferation and migration of colorectal cancer cells in vitro and in vivo.
abstract: The expression patterns of the long non-coding RNA Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) have not been investigated in the context of cancer. In this study, we aim to investigate the NNT-AS1 expression level in colorectal cancer (CRC) patients and its potential roles in tumor biology. We measured the expression of NNT-AS1 in 70 paired tumor tissues and adjacent normal tissues. NNT-AS1 was expressed higher in tumor tissues than that in adjacent noncancer tissues, and higher expression of NNT-AS1 was significantly correlated with lymph node metastasis (Yes vs. No, P=0.004), TNM stage (I/II vs. III/IV, P=0.004), vessel invasion (Yes vs. No, P=0.002) and differentiation (well and moderate vs. poor, P=0.008). Multivariate analyses revealed that NNT-AS1 expression was an independent predictor of overall survival (P=0.0174) and progression free survival (P=0.0132) for CRC. Knockdown of NNT-AS1 using small interfering RNA (siRNA) significantly impaired CRC cell proliferation, migration and invasion in vitro and silencing NNT-AS1 also suppressed tumor growth and metastasis in nude mice. The western blot experiments revealed that silencing NNT-AS1 inhibited epithelial-mesenchymal transition (EMT) and inactivated MAPK/Erk signaling pathway in CRC cell lines. In conclusion, our studies implied that NNT-AS1 may involve in the development and progression of CRC via its regulation of cell proliferation, migration, and invasion by NNT-AS1-mediated activating of MAPK/Erk signaling pathway and EMT. NNT-AS1 may be a useful diagnostic and prognostic biomarker and a potential therapeutic target in CRC patients.
authors.affiliation: Department of Oncology, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Medical Research Center, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Oncology, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Oncology, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Oncology, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Yizhang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Oncology, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Medical Research Center, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Medical Research Center, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wen
authors.affiliation: Department of Respiratory Medicine, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Oncology, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: An
authors.affiliation: Department of Oncology, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Feng
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering
keywords: MAPK/Erk; NNT-AS1; biomarker; colorectal cancer; long non-coding RNA