Department of Stomatology, Affiliated Hospital of Inner Mongolia University for Nationalities, No.1742, Huolinhe Street, Tongliao, 028000, Inner Mongolia, PR China.
Arch Oral Biol. 2021 Jun;126:105114. doi: 10.1016/j.archoralbio.2021.105114. Epub 2021 Mar 31.
The aim of this study was to investigate the effects of long non-coding RNA (lncRNA) HOXA10 antisense RNA (HOXA10-AS) on the properties of oral squamous cell carcinoma (OSCC) stem cells and the molecular mechanism.
Tumor and the paracancerous tissues were collected from 83 patients with OSCC. OSCC stem cells were extracted from a human OSCC cell line Tca8113. Silencing of HOXA10-AS was introduced in stem cells and then the malignant behaviors of cells were determined. The target transcripts of HOXA10-AS were predicted using integrated bioinformatics analyses. The interactions among HOXA10-AS, microRNA (miR)-29a and MCL-1 were validated, and their functions in stem cell behaviors in vivo and in vitro were explored.
HOXA10-AS and MCL-1 were highly expressed while miR-29a was poorly expressed in the collected tumor tissues and the extracted OSCC stem cells. High expression of HOXA10-AS and MCL-1, while poor expression of miR-29a was relevant to poor prognosis in patients. Silencing of HOXA10-AS suppressed proliferation and tumor sphere formation ability of stem cells, and it reduced growth and metastasis of tumors in animals. HOXA10-AS served as a sponge for miR-29a and upregulated MCL-1 mRNA expression. Inhibition of miR-29a promoted, while silencing of MCL-1 suppressed the malignant behaviors of OSCC stem cells. In addition, HOXA-10-AS and MCL-1 were found to activate the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway.
This study evidenced that HOXA10-AS enhances the stem cell property of OSCC stem cells through the miR-29a/MCL-1/PI3K/AKT axis.
本研究旨在探讨长链非编码 RNA（lncRNA）HOXA10 反义 RNA（HOXA10-AS）对口腔鳞状细胞癌（OSCC）干细胞特性的影响及其分子机制。
收集 83 例 OSCC 患者的肿瘤及癌旁组织。从人 OSCC 细胞系 Tca8113 中提取 OSCC 干细胞。沉默 HOXA10-AS 后，检测细胞的恶性行为。采用整合生物信息学分析预测 HOXA10-AS 的靶转录本。验证 HOXA10-AS、微小 RNA（miR）-29a 和 MCL-1 之间的相互作用，并探讨它们在体内和体外干细胞行为中的功能。
在收集的肿瘤组织和提取的 OSCC 干细胞中，HOXA10-AS 和 MCL-1 高表达，而 miR-29a 低表达。HOXA10-AS 和 MCL-1 高表达、miR-29a 低表达与患者预后不良相关。沉默 HOXA10-AS 可抑制干细胞的增殖和肿瘤球形成能力，并降低动物肿瘤的生长和转移。HOXA10-AS 作为 miR-29a 的海绵，上调 MCL-1 mRNA 表达。抑制 miR-29a 促进，而沉默 MCL-1 抑制 OSCC 干细胞的恶性行为。此外，还发现 HOXA10-AS 和 MCL-1 激活了磷脂酰肌醇 3-激酶/蛋白激酶 B（PI3K/AKT）信号通路。
本研究表明，HOXA10-AS 通过 miR-29a/MCL-1/PI3K/AKT 轴增强 OSCC 干细胞的干细胞特性。
