Promotion of LncRNA HOXA11-AS on the proliferation of hepatocellular carcinoma by regulating the expression of LATS1

J. Yu, J.-F. Hong, J. Kang, L.-H. Liao, C.-D. Li

Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China. fjzylcd@126.com

---

• Oncology

OBJECTIVE: To investigate the expression levels of lncRNA HOXA11-AS in HCC tissues and cells, and to explore its biological role in the development and progression of HCC.

PATIENTS AND METHODS: We detected the relative expression level of HOXA11-AS in 72 HCC tissues and cells by the real-time quantitative PCR (qRT-PCR) assay. After interference with HOXA11-AS expression in HCC cells, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clone formation, flow cytometry and an established nude mice transplanted tumor model were used to detect the biological behavior of HCC cells. qRT-PCR and Western blotting assays were used to detect the expression level of large tumor suppressor kinases 1 (LATS1). The subcellular localization of HOXA11-AS in HCC was detected by separating nuclei from the cytoplasm. The molecular mechanism of HOXA11-AS was regulated by ribonucleoprotein immunoprecipitation-microarray (RIP-Chip) experiments.

RESULTS: qRT-PCR assays showed that HOXA11-AS was relatively highly expressed in HCC tissues and cells. In vivo and in vitro experiments showed that HOXA11-AS could inhibit the proliferation of HCC cells, promote their apoptosis and retard the cell cycle progression from G1 to G0 phase. qRT-PCR and Western blotting assays results showed that LATS1 genes were the downstream target genes of HOXA11-AS. RIP and CHIP experiments showed that HOXA11-AS inhibited the expression of LATS1 genes by binding enhancer of zeste homolog 2 (EZH2) proteins.

CONCLUSIONS: HOXA11-AS inhibited the malignant transcription of the LATS1 genes and promoted the malignant proliferation of HCC cells. Interactions among HOXA11-AS, PRC2, and LATS1 may provide a new target for the treatment of HCC.

Free PDF Download