LncRNA HOXA-AS2 Promotes Tumor Progression by Suppressing miR-567 Expression in Oral Squamous Cell Carcinoma
Rui Chen,1 Xi Wang,2,3 Shixian Zhou,2,4 Zongyue Zeng2 1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical Un...
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Dove Medical Press
2021-07-01
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| Series: | Cancer Management and Research |
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| Online Access: | https://www.dovepress.com/lncrna-hoxa-as2-promotes-tumor-progression-by-suppressing-mir-567-expr-peer-reviewed-fulltext-article-CMAR |
| _version_ | 1818738173372530688 |
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| author | Chen R Wang X Zhou S Zeng Z |
| author_facet | Chen R Wang X Zhou S Zeng Z |
| author_sort | Chen R |
| collection | DOAJ |
| description | Rui Chen,1 Xi Wang,2,3 Shixian Zhou,2,4 Zongyue Zeng2 1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 4Department of Pathology, Central Hospital of Jiangjin District, Chongqing, 402260, People’s Republic of ChinaCorrespondence: Zongyue ZengDepartment of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaTel +86 23-8895-5532Email zengzongyue@126.comIntroduction: 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.Keywords: LncRNA HOXA-AS2, MiR-567, CDK8, Oral squamous cell carcinoma, Tumor progression |
| first_indexed | 2024-12-18T01:04:44Z |
| format | Article |
| id | doaj.art-07d573ffd03d4d6e802bb71ee5d23aab |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-18T01:04:44Z |
| publishDate | 2021-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-07d573ffd03d4d6e802bb71ee5d23aab2022-12-21T21:26:16ZengDove Medical PressCancer Management and Research1179-13222021-07-01Volume 135443545566726LncRNA HOXA-AS2 Promotes Tumor Progression by Suppressing miR-567 Expression in Oral Squamous Cell CarcinomaChen RWang XZhou SZeng ZRui Chen,1 Xi Wang,2,3 Shixian Zhou,2,4 Zongyue Zeng2 1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 4Department of Pathology, Central Hospital of Jiangjin District, Chongqing, 402260, People’s Republic of ChinaCorrespondence: Zongyue ZengDepartment of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaTel +86 23-8895-5532Email zengzongyue@126.comIntroduction: 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.Keywords: LncRNA HOXA-AS2, MiR-567, CDK8, Oral squamous cell carcinoma, Tumor progressionhttps://www.dovepress.com/lncrna-hoxa-as2-promotes-tumor-progression-by-suppressing-mir-567-expr-peer-reviewed-fulltext-article-CMARlncrna hoxa-as2mir-567cdk8oral squamous cell carcinomatumor progression |
| spellingShingle | Chen R Wang X Zhou S Zeng Z LncRNA HOXA-AS2 Promotes Tumor Progression by Suppressing miR-567 Expression in Oral Squamous Cell Carcinoma Cancer Management and Research lncrna hoxa-as2 mir-567 cdk8 oral squamous cell carcinoma tumor progression |
| title | LncRNA HOXA-AS2 Promotes Tumor Progression by Suppressing miR-567 Expression in Oral Squamous Cell Carcinoma |
| title_full | LncRNA HOXA-AS2 Promotes Tumor Progression by Suppressing miR-567 Expression in Oral Squamous Cell Carcinoma |
| title_fullStr | LncRNA HOXA-AS2 Promotes Tumor Progression by Suppressing miR-567 Expression in Oral Squamous Cell Carcinoma |
| title_full_unstemmed | LncRNA HOXA-AS2 Promotes Tumor Progression by Suppressing miR-567 Expression in Oral Squamous Cell Carcinoma |
| title_short | LncRNA HOXA-AS2 Promotes Tumor Progression by Suppressing miR-567 Expression in Oral Squamous Cell Carcinoma |
| title_sort | lncrna hoxa as2 promotes tumor progression by suppressing mir 567 expression in oral squamous cell carcinoma |
| topic | lncrna hoxa-as2 mir-567 cdk8 oral squamous cell carcinoma tumor progression |
| url | https://www.dovepress.com/lncrna-hoxa-as2-promotes-tumor-progression-by-suppressing-mir-567-expr-peer-reviewed-fulltext-article-CMAR |
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