Promotive effects of HOXA10 antisense RNA on the stemness of oral squamous cell carcinoma stem cells through a microRNA-29a/MCL-1/phosphatidyl inositol 3-kinase/protein kinase B axis

Objective: 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. Design: 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. Results: 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. Conclusion: This study evidenced that HOXA10-AS enhances the stem cell property of OSCC stem cells through the miR-29a/MCL-1/PI3K/AKT axis.