PMID- 31978895 OWN - NLM STAT- MEDLINE DCOM- 20210111 LR - 20210111 IS - 1945-4589 (Electronic) IS - 1945-4589 (Linking) VI - 12 IP - 2 DP - 2020 Jan 24 TI - AR-induced ZEB1-AS1 represents poor prognosis in cholangiocarcinoma and facilitates tumor stemness, proliferation and invasion through mediating miR-133b/HOXB8. PG - 1237-1255 LID - 10.18632/aging.102680 [doi] AB - Zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) has displayed vital regulatory function in various tumors. However, the biological function of ZEB1-AS1 in cholangiocarcinoma (CCA) remains unclear. In this study, we confirmed that ZEB1-AS1 expression was increased in CCA tissues and cells, respectively. Upregulated ZEB1-AS1 was related to lymph node invasion, advanced TNM stage and poor survival of CCA patients. ZEB1-AS1 exhibited high sensitivity and specificity to be an independent poor prognostic factor of patients with CCA. Functionally, knocking down ZEB1-AS1 attenuated tumor cell stemness, restrained cellular viability in vitro and in vivo, and inhibited CCA cell migration and invasion by reversing epithelial-mesenchymal transition. For the mechanism, androgen receptor (AR) directly promoted ZEB1-AS1 expression, and further ZEB1-AS1 increased oncogene homeobox B8 (HOXB8) by sponging miR-133b. In addition, malignant phenotypes of CCA promoted by ZEB1-AS1 dysregulation were rescued separately through interfering miR-133b and HOXB8, suggesting AR/ZEB1-AS1/miR-133b/HOXB8 exerted crucial functions in tumorigenesis and progression of CCA. FAU - Jiang, Xingming AU - Jiang X AD - Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Li, Jinglin AU - Li J AD - Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Wang, Weina AU - Wang W AD - Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Hu, Zengtao AU - Hu Z AD - Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Guan, Canghai AU - Guan C AD - Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Zhao, Yuqiao AU - Zhao Y AD - Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Li, Wenzhi AU - Li W AD - Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Cui, Yunfu AU - Cui Y AD - Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200124 PL - United States TA - Aging (Albany NY) JT - Aging JID - 101508617 RN - 0 (AR protein, human) RN - 0 (HOXB8 protein, human) RN - 0 (Homeodomain Proteins) RN - 0 (MIRN133 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (Receptors, Androgen) SB - IM MH - Bile Duct Neoplasms/*etiology/*metabolism/mortality/pathology MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Cell Proliferation MH - Cell Survival/genetics MH - Cell Transformation, Neoplastic/genetics/metabolism MH - Cholangiocarcinoma/*etiology/*metabolism/mortality/pathology MH - Epithelial-Mesenchymal Transition/genetics MH - Gene Expression Regulation, Neoplastic MH - Homeodomain Proteins/*genetics MH - Humans MH - MicroRNAs/*genetics MH - Neoplasm Metastasis MH - Neoplasm Staging MH - Neoplastic Stem Cells/metabolism MH - Prognosis MH - RNA Interference MH - RNA, Long Noncoding/*genetics MH - ROC Curve MH - Receptors, Androgen/*metabolism MH - Signal Transduction PMC - PMC7053610 OTO - NOTNLM OT - HOXB8 OT - ZEB1-AS1 OT - cholangiocarcinoma OT - miR-133b OT - prognosis COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interest. EDAT- 2020/01/25 06:00 MHDA- 2021/01/12 06:00 PMCR- 2020/01/31 CRDT- 2020/01/25 06:00 PHST- 2019/10/04 00:00 [received] PHST- 2019/12/25 00:00 [accepted] PHST- 2020/01/25 06:00 [pubmed] PHST- 2021/01/12 06:00 [medline] PHST- 2020/01/25 06:00 [entrez] PHST- 2020/01/31 00:00 [pmc-release] AID - 102680 [pii] AID - 10.18632/aging.102680 [doi] PST - ppublish SO - Aging (Albany NY). 2020 Jan 24;12(2):1237-1255. doi: 10.18632/aging.102680. Epub 2020 Jan 24.