LncRNA HOXA-AS2 Promotes Tumor Progression by Suppressing miR-567 Expression in Oral Squamous Cell Carcinoma

Abstract

Introduction: Growing evidence suggests that long non-coding RNAs (lncRNAs), such as lncRNA HOXA-AS2, are critical regulators involved in human cancer. However, the biological functions and detailed mechanisms underlying how lncRNA HOXA-AS2 affects oral squamous cell carcinoma (OSCC) remain unexplored. Methods: The expression of lncRNA HOXA-AS2 and miR-567 was determined in OSCC cell lines and clinical tissues by quantitative real-time PCR (qRT-PCR). Target site prediction and luciferase report assays were used to explore their potential interaction and binding sites between lncRNA HOXA-AS2 and miR-567. Overexpression or silencing expression of lncRNA HOXA-AS2 was performed to confirm that miR-567 was suppressed by lncRNA HOXA-AS2. WST-1 assay, crystal staining assay, and cell cycle analysis were used to assess the cell viability and proliferation ability. The target gene of miR-567 was predicted by Targetscan and validated by luciferase report assay as well as qRT-PCR and Western Blot. Xenograft nude mice model was done to demonstrate that lncRNA HOXA-AS2 promoted cell proliferation via targeting miR-567/CDK8 in vivo. Results: LncRNA HOXA-AS2 was up-regulated in OSCC cells and tissues with the expression of miR-567 decreased. The tissue lncRNA HOXA-AS2 expression was found to positively correlate with the TNM stage and lymph node metastasis of OSCC patients. In terms of the mechanism, we found that lncRNA HOXA-AS2 negatively regulates miR-567 expression via a direct interaction. Functionally, overexpression of lncRNA HOXA-AS2 significantly promoted OSCC cell proliferation, while knockdown of lncRNA HOXA-AS2 significantly inhibited it. We also observed that miR-567 directly targets the 3ʹ UTR of CDK8. Moreover, silencing lncRNA HOXA-AS2 inhibited tumor growth with the expression of miR-567 increased and CDK8 decreased in vivo. Conclusion:LncRNA HOXA-AS2 was up-regulated in OSCC, and its up-regulation correlated with poor clinical outcomes. The lncRNA also promoted OSCC cell proliferation by directly binding to miR-567, leading to an increase in CDK8 expression. The potential prognostic value of lncRNA HOXA-AS2 should be explored in future studies.

Prognostic Value of lncRNA DRAIC and miR-3940-3p in Lung Adenocarcinoma and Their Effect on Lung Adenocarcinoma Cell Progression

“… 35 Many studies have demonstrated lncRNAs involved in competitive regulatory interactions and can act as microRNA decoys to modulate gene expression, which is known as ceRNA. 36 , 37 In this study, lnc DRAIC has potential binding sites with miR-3940-3p, and the siRNA of lnc DRAIC can significantly increase the expression level of miR-3940-3p. Dual-luciferase reporter assay confirmed the binding between lnc DRAIC and miR-3940-3p.…”

CDK3, CDK5 and CDK8 Proteins as Prognostic and Potential Biomarkers in Colorectal Cancer Patients

“…CDK3 has been reported to promote myoblast cell proliferation; 31 Yue et al showed that CDK5 promotes the proliferation of medullary thyroid carcinoma cells; 32 in addition, Chen et al showed that the promotion of OSCC cell proliferation by direct binding of miR-567 leads to increased CDK8 expression. 33 These previous findings suggest that CDK3, CDK5 and CDK8 is an oncogene.…”

HOXA-AS2 may predict the prognosis of solid tumors among Chinese patients: A meta-analysis and bioinformatic analysis

“…A total of 18 articles including 1181 patients were included, and the cancer types included gastric cancer ( 24 ), colorectal cancer (CRC) ( 29 , 40 ), hepatocellular carcinoma(HCC) ( 26 , 27 , 41 ), breast cancer ( 18 ), non-small cell lung cancer (NSCLC) ( 19 , 22 ), prostate cancer ( 31 ), osteosarcoma ( 36 , 37 ), bladder cancer ( 30 ), oral squamous cell carcinoma (OSCC) ( 13 ), papillary thyroid cancer (PTC) ( 15 , 16 ), cervical cancer ( 35 ) and glioma ( 47 ). The publication years were from 2015 to 2021, and all patients were from China.…”

“…HOXA-AS2 is a 1048-bp long noncoding RNA located on human chromosome 7p15.2 between the HOXA3 and HOXA4 genes in the HOXA cluster ( 11 ). In recent years, an increasing number of publications have shown that HOXA-AS2 is highly expressed in diverse malignancies, including oral squamous cell carcinoma ( 12 , 13 ), nasopharyngeal carcinoma ( 14 ), thyroid cancer ( 15 , 16 ), breast cancer ( 17 , 18 ), lung cancer ( 19 – 22 ), gallbladder carcinoma ( 23 ), gastric cancer ( 24 , 25 ), hepatocellular carcinoma ( 26 , 27 ), pancreatic cancer ( 28 ), colorectal cancer ( 29 ), bladder cancer ( 30 ), prostate cancer ( 31 ), ovarian cancer ( 32 ), endometrial cancer ( 33 ), cervical cancer ( 34 , 35 ), osteosarcoma ( 36 , 37 ) and glioblastoma ( 38 ). Cell function tests showed that high HOXA-AS2 expression can promote the proliferation and invasion of cancer cells, inhibit apoptosis, and affect the cancer cell cycle ( 21 , 32 ).…”