Department of Pediatrics, Shiyan Taihe Hospital, Shiyan, Hubei, China.
Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Army Medical University, Chinese People's Liberation Army, Shapingba, Chongqing, China.
J Cell Biochem. 2019 Sep;120(9):15941-15951. doi: 10.1002/jcb.28871. Epub 2019 May 17.
HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11-AS), a newly identified long noncoding RNAs, is involved in the carcinogenic process of several human tumors. However, the role of HOXA11-AS in liver cancer progression is not well understood.
This study used liver cancer tissues and cell lines (CSQT-2 and HCCLM3) to explore the potential mechanism of HOXA11-AS. Quantitative real-time polymerase chain reaction and Western blot were applied to evaluate the bio-molecules expression. Bioinformatics analysis, RNA pull down and luciferase report assay were applied to determine the molecules bind. MTT, transwell, and wound healing assay were used to measure the cell growth situation.
HOXA11-AS was highly expressed in liver cancer tissues and cell lines, which was closely related with poor prognosis in patients with liver cancer. HOXA11-AS could act as a competing endogenous RNA for miR-15a-3p. Besides, miR-15a-3p negatively controlled its target molecule signal transducer and activator of transcription 3 (STAT3). Furthermore, a linear regression analysis and biological experiments showed a positive correlation between HOAX11-AS and STAT3. Moreover, HOAX11-AS overexpression activated the Janus kinase (JAK)-STAT pathway and thus promoted the growth, migration, and invasion of liver cancer cells, which might be through regulating miR-15a-3p/STAT3 axis.
Our study suggested that HOAX11-AS could regulate the JAK-STAT signaling pathway by miR-15a-3p/STAT3 axis to promote the progression of liver cancer. Thus, HOXA11-AS may be regarded as an effective biomarker with diagnostic, prognostic, and therapeutic potentials for liver cancer.
同源盒 A11（HOXA11）反义 RNA（HOXA11-AS）是一种新发现的长非编码 RNA，参与了多种人类肿瘤的致癌过程。然而，HOXA11-AS 在肝癌进展中的作用尚不清楚。
本研究使用肝癌组织和细胞系（CSQT-2 和 HCCLM3）来探讨 HOXA11-AS 的潜在机制。采用定量实时聚合酶链反应和 Western blot 来评估生物分子的表达。应用生物信息学分析、RNA 下拉和荧光素酶报告实验来确定结合分子。采用 MTT、Transwell 和划痕愈合实验来测量细胞的生长情况。
HOXA11-AS 在肝癌组织和细胞系中高表达，与肝癌患者的不良预后密切相关。HOXA11-AS 可以作为 miR-15a-3p 的竞争性内源性 RNA。此外，miR-15a-3p 负调控其靶分子信号转导和转录激活因子 3（STAT3）。此外，线性回归分析和生物学实验表明，HOAX11-AS 与 STAT3 之间存在正相关。此外，HOAX11-AS 的过表达激活了 Janus 激酶（JAK）-STAT 通路，从而促进了肝癌细胞的生长、迁移和侵袭，这可能是通过调节 miR-15a-3p/STAT3 轴实现的。
本研究表明，HOAX11-AS 可以通过 miR-15a-3p/STAT3 轴调节 JAK-STAT 信号通路，促进肝癌的进展。因此，HOAX11-AS 可能作为一种有效的生物标志物，具有诊断、预后和治疗肝癌的潜力。
