HIF-1α-activated long non-coding RNA KDM4A-AS1 promotes hepatocellular carcinoma progression via the miR-411-5p/KPNA2/AKT pathway

• DOI: 10.1038/s41419-021-04449-2
• Publication Date: 2021-12-13T10:06:57Z
• Authors: Tianxiang Chen; Runkun Liu; Yongshen Niu; Huanye Mo; Hao Wang; Ye Lu; Liang Wang; Liankang Sun; Yufeng Wang; Kangsheng Tu; Qingguang Liu
• Keywords: alpha Karyopherins; 0301 basic medicine; Jumonji Domain-Containing Histone Demethylases; Carcinoma, Hepatocellular; QH573-671; Liver Neoplasms; Hypoxia-Inducible Factor 1, alpha Subunit; Article; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Disease Progression; Humans; RNA, Long Noncoding; Cytology; Hypoxia; Proto-Oncogene Proteins c-akt; Cell Proliferation

Abstract Hepatocellular carcinoma (HCC) is the most common type of liver cancer with poor clinical outcomes. Long non-coding RNAs (lncRNAs) are extensively involved in tumorigenesis and progression HCC. However, more investigations should be carried out on novel lncRNAs their effects Here we identified a lncRNA KDM4A-AS1, which was aberrantly overexpressed HCC tissues, associated unfavorable features prognosis patients. KDM4A-AS1 promoted cell proliferation, migration, invasion vitro contributed to growth lung metastasis vivo. Mechanistically, inversely modulated by miR-411-5p at post-transcriptional level facilitated Karyopherin α2 (KPNA2) expression competitively binding miR-411-5p, thereby activating AKT pathway. KPNA2 silencing, overexpression, inhibitor (MK2206) consistently reversed KDM4A-AS1-enhanced mobility, EMT cells. as hypoxia-responsive gene transactivated hypoxia-inducible factor 1α (HIF-1α) In turn, regulated HIF-1α through KPNA2/AKT signaling Hence, this study revealed lncRNA, via KDM4A-AS1/KPNA2/HIF-1α loop. Our findings provide promising prognostic therapeutic target for