title: The long noncoding RNA HOXA11 antisense induces tumor progression and stemness maintenance in cervical cancer.
abstract: Recent research has focused on the impact of long noncoding RNA (lncRNA) in cervical carcinogenesis. However, whether HOXA11 antisense (HOXA11-AS) is involved in cervical cancer remains to be elucidated. In the present study, we examined HOXA11-AS expression levels in cervical cancer patients and determined the relationships between HOXA11-AS expression and clinicopathological factors. We also investigated the bio-functional consequences of HOXA11-AS overexpression both in vitro and in vivo. HOXA11-AS expression was significantly greater in tissues from patients with cervical cancer than in control patients (P<0.001). Multivariate analysis showed that high HOXA11-AS was an independent prognosticator of overall survival (Hazard ratio=2.450, P=0.032). HOXA11-AS overexpression enhanced cell proliferation, migration, and tumor invasion in vitro, whereas HOXA11-AS knockdown inhibited these biologic aggressive features. These adverse changes were accompanied by characteristics of epithelial-mesenchymal transition (EMT). In vivo xenograft experiments using the siHOXA11-AS-transfected HeLa cells revealed that HOXA11-AS strongly induced tumor growth. Furthermore, we found that HOXA11-AS knockdown decreased cancer stemness and triggered the EMT program. In conclusion, HOXA11-AS overexpression correlated with poor survival in patients with cervical cancer. Thus, HOXA11-AS may be a pivotal target for exploring novel cervical cancer therapeutics.
authors: Institute of Women's Life Medical Science, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.
authors: Hee Jung
authors: HJ
authors: Kim
authors: Institute of Women's Life Medical Science, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.|Department of Obstetrics and Gynecology, Yonsei University Graduate School, Seoul, Korea.
authors: Kyung Jin
authors: KJ
authors: Eoh
authors: Institute of Women's Life Medical Science, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.
authors: Lee Kyung
authors: LK
authors: Kim
authors: Institute of Women's Life Medical Science, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.
authors: Eun Ji
authors: EJ
authors: Nam
authors: Department of Pathology, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors: Sun Och
authors: SO
authors: Yoon
authors: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea.
authors: Kun-Hong
authors: KH
authors: Kim
authors: Department of Obstetrics and Gynecology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
authors: Jae Kwan
authors: JK
authors: Lee
authors: Institute of Women's Life Medical Science, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.
authors: Sang Wun
authors: SW
authors: Kim
authors: Institute of Women's Life Medical Science, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.
authors: Young Tae
authors: YT
authors: Kim
mesh_terms: D000328:Adult; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D062085:RNA, Long Noncoding; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: HOXA11 antisense; cervical cancer; invasion; long noncoding RNA; prognosis