SNHG12/miR-326/E2F1 feedback loop facilitates the progression of oral squamous cell carcinoma
Yue Yin
Department of Stomatology, North China University of Science and Technology Affiliated Hospital, Tangshan, China
Contribution: Conceptualization, Resources, Software
Search for more papers by this authorCorresponding Author
Yingyun Tan
Stomatological Hospital of Chongqing Medical University, Chongqing, China
Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
Correspondence
Yingyun Tan, Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, No. 426 Songshi North Road, Yubei District, Chongqing 400016, China.
Email: [email protected]
Contribution: Data curation, Formal analysis, Funding acquisition, Writing - original draft
Search for more papers by this authorYuan Yao
Department of Stomatology, North China University of Science and Technology Affiliated Hospital, Tangshan, China
Contribution: Investigation, Methodology
Search for more papers by this authorNa Lu
Department of Stomatology, North China University of Science and Technology Affiliated Hospital, Tangshan, China
Contribution: Project administration, Supervision, Validation
Search for more papers by this authorFugui Zhang
Stomatological Hospital of Chongqing Medical University, Chongqing, China
Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
Contribution: Visualization, Writing - review & editing
Search for more papers by this authorYue Yin
Department of Stomatology, North China University of Science and Technology Affiliated Hospital, Tangshan, China
Contribution: Conceptualization, Resources, Software
Search for more papers by this authorCorresponding Author
Yingyun Tan
Stomatological Hospital of Chongqing Medical University, Chongqing, China
Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
Correspondence
Yingyun Tan, Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, No. 426 Songshi North Road, Yubei District, Chongqing 400016, China.
Email: [email protected]
Contribution: Data curation, Formal analysis, Funding acquisition, Writing - original draft
Search for more papers by this authorYuan Yao
Department of Stomatology, North China University of Science and Technology Affiliated Hospital, Tangshan, China
Contribution: Investigation, Methodology
Search for more papers by this authorNa Lu
Department of Stomatology, North China University of Science and Technology Affiliated Hospital, Tangshan, China
Contribution: Project administration, Supervision, Validation
Search for more papers by this authorFugui Zhang
Stomatological Hospital of Chongqing Medical University, Chongqing, China
Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
Contribution: Visualization, Writing - review & editing
Search for more papers by this authorYue Yin and Yingyun Tan are cofirst authors.
Abstract
Oral squamous cell carcinoma (OSCC) is a kind of common malignant tumor worldwide. An increasing number of researches have validated that long non-coding RNAs (lncRNAs) are closely associated with the occurrence and development of multiple diseases, including cancers. However, the role of lncRNA SNHG12 in OSCC was largely unknown. In present study, qRT-PCR manifested the upregulation of SNHG12 expression in OSCC tissues and cells. Suppression of SNHG12 inhibited cell proliferation, migration, invasion, and EMT process in OSCC. Additionally, SNHG12 depletion also attenuated OSCC tumor growth in vivo. Thereafter, E2F1 was found to be a transcription factor of SNHG12 to stimulate its expression. More interestingly, SNHG12 deficiency reduced E2F1 expression in turn. MiR-326 was found to be shared between SNHG12 and E2F1. Besides, SNHG12 augmented E2F1 in OSCC through miR-326 sequestration. Finally, rescue assays demonstrated that overexpressed E2F1 restored the inhibitory effect resulted from SNHG12 silence, indicating that SNHG12 promoted the progression of OSCC by E2F1-dependent way. This research unveiled that SNHG12/miR-326/E2F1 feedback loop facilitated OSCC progression, which shed new light on therapeutic methods in OSCC.
CONFLICT OF INTEREST
The authors declare that there are no competing interests in this study.
REFERENCES
- Bozec, A., Peyrade, F., Fischel, J. L., & Milano, G. (2009). Emerging molecular targeted therapies in the treatment of head and neck cancer. Expert Opinion on Emerging Drugs, 14(2), 299–310.
- Bucha, S., Mukhopadhyay, D., & Bhattacharyya, N. P. (2019). E2F1 activates MFN2 expression by binding to the promoter and decreases mitochondrial fission and mitophagy in HeLa cells. The FEBS Journal, 286(22), 4525–4541. https://doi.org/10.1111/febs.14980
- Cao, L., Wang, J., & Wang, P. Q. (2016). MiR-326 is a diagnostic biomarker and regulates cell survival and apoptosis by targeting Bcl-2 in osteosarcoma. Biomedicine & Pharmacotherapy, 84, 828–835. https://doi.org/10.1016/j.biopha.2016.10.008
- Chen, F., Qi, S., Zhang, X., Wu, J., Yang, X., & Wang, R. (2019). lncRNA PLAC2 activated by H3K27 acetylation promotes cell proliferation and invasion via the activation of Wnt/betacatenin pathway in oral squamous cell carcinoma. International Journal of Oncology, 54(4), 1183–1194. https://doi.org/10.3892/ijo.2019.4707
- Chen, H., Chen, J., Zhao, L., Song, W., Xuan, Z., Chen, J., … Zheng, S. (2019). CDCA5, Transcribed by E2F1, promotes oncogenesis by enhancing cell proliferation and inhibiting apoptosis via the AKT pathway in hepatocellular carcinoma. J Cancer, 10(8), 1846–1854. https://doi.org/10.7150/jca.28809
- Chen, Z., Tao, Q., Qiao, B., & Zhang, L. (2019). Silencing of LINC01116 suppresses the development of oral squamous cell carcinoma by up-regulating microRNA-136 to inhibit FN1. Cancer Management and Research, 11, 6043–6059. https://doi.org/10.2147/cmar.S197583
- Chi, A. C., Day, T. A., & Neville, B. W. (2015). Oral cavity and oropharyngeal squamous cell carcinoma–an update. CA: A Cancer Journal for Clinicians, 65(5), 401–421. https://doi.org/10.3322/caac.21293
- Guo, Y., Ma, Y., Hu, X., Song, R., Zhu, L., & Zhong, M. (2018). Long non-coding RNA CEBPA-AS1 correlates with poor prognosis and promotes tumorigenesis via CEBPA/Bcl2 in oral squamous cell carcinoma. Cancer Biology & Therapy, 19(3), 205–213. https://doi.org/10.1080/15384047.2017.1416276
- Jin, L. J., Lamster, I. B., Greenspan, J. S., Pitts, N. B., Scully, C., & Warnakulasuriya, S. (2016). Global burden of oral diseases: Emerging concepts, management and interplay with systemic health. Oral Diseases, 22(7), 609–619. https://doi.org/10.1111/odi.12428
- Kessler, P., Grabenbauer, G., Leher, A., Bloch-Birkholz, A., Vairaktaris, E., & Neukam, F. W. (2008). Neoadjuvant and adjuvant therapy in patients with oral squamous cell carcinoma. British Journal of Oral and Maxillofacial Surgery, 46(1), 1–5. https://doi.org/10.1016/j.bjoms.2007.08.006
- Leemans, C. R., Braakhuis, B. J. M., & Brakenhoff, R. H. (2011). The molecular biology of head and neck cancer. Nature Reviews Cancer, 11(1), 9–22. https://doi.org/10.1038/nrc2982
- Liang, X., Li, Z., Men, Q., Li, Y., Li, H., & Chong, T. (2018). miR-326 functions as a tumor suppressor in human prostatic carcinoma by targeting Mucin1. Biomedicine & Pharmacotherapy, 108, 574–583. https://doi.org/10.1016/j.biopha.2018.09.053
- Lin, D., Shi, Y., Hu, Y., Du, X., & Tu, G. (2019). miR3293p regulates neural stem cell proliferation by targeting E2F1. Molecular Medicine Reports, 19(5), 4137–4146. https://doi.org/10.3892/mmr.2019.10096
- Lu, T., Liu, H., & You, G. (2018). Long non-coding RNA C5orf66-AS1 prevents oral squamous cell carcinoma through inhibiting cell growth and metastasis. International Journal of Molecular Medicine, 42(6), 3291–3299. https://doi.org/10.3892/ijmm.2018.3913
- Qi, X., Zhang, D.-H., Wu, N., Xiao, J.-H., Wang, X., & Ma, W. (2015). ceRNA in cancer: Possible functions and clinical implications. Journal of Medical Genetics, 52(10), 710–718. https://doi.org/10.1136/jmedgenet-2015-103334
- Ribeiro, K. C., Kowalski, L. P., & Latorre, M. R. (2000). Impact of comorbidity, symptoms, and patients' characteristics on the prognosis of oral carcinomas. Archives of Otolaryngology – Head and Neck Surgery, 126(9), 1079–1085. https://doi.org/10.1001/archotol.126.9.1079
- Sasahira, T., & Kirita, T. (2018). Hallmarks of cancer-related newly prognostic factors of oral squamous cell carcinoma. International Journal of Molecular Sciences, 19(8), 2413. https://doi.org/10.3390/ijms19082413
- Shao, T.-R., Zheng, Z.-N., Chen, Y.-C., Wu, Q.-Q., Huang, G.-Z., Li, F., … Lv, X.-Z. (2019). LncRNA AC007271.3 promotes cell proliferation, invasion, migration and inhibits cell apoptosis of OSCC via the Wnt/β-catenin signaling pathway. Life Sciences, 239, 117087. https://doi.org/10.1016/j.lfs.2019.117087
- Sun, C.-C., Zhang, L., Li, G., Li, S.-J., Chen, Z.-L., Fu, Y.-F., … Li, D.-J. (2017). The lncRNA PDIA3P interacts with miR-185-5p to modulate oral squamous cell carcinoma progression by targeting cyclin D2. Molecular Therapy. Nucleic Acids, 9, 100–110. https://doi.org/10.1016/j.omtn.2017.08.015
- Ulitsky, I., & Bartel, D. P. (2013). lincRNAs: Genomics, evolution, and mechanisms. Cell, 154(1), 26–46. https://doi.org/10.1016/j.cell.2013.06.020
- Wang, J. Z., Xu, C. L., Wu, H., & Shen, S. J. (2017). LncRNA SNHG12 promotes cell growth and inhibits cell apoptosis in colorectal cancer cells. Brazilian Journal of Medical and Biological Research, 50(3), e6079. https://doi.org/10.1590/1414-431x20176079
- Wang, O., Yang, F., Liu, Y., Lv, L., Ma, R., Chen, C., … Zhang, X. (2017). C-MYC-induced upregulation of lncRNA SNHG12 regulates cell proliferation, apoptosis and migration in triple-negative breast cancer. American Journal of Translational Research, 9(2), 533–545.
- Wang, P., Chen, D., Ma, H., & Li, Y. (2017). LncRNA SNHG12 contributes to multidrug resistance through activating the MAPK/Slug pathway by sponging miR-181a in non-small cell lung cancer. Oncotarget, 8(48), 84086–84101. https://doi.org/10.18632/oncotarget.20475
- Wang, R., Chen, X., Xu, T., Xia, R., Han, L., Chen, W., … Shu, Y. (2016). MiR-326 regulates cell proliferation and migration in lung cancer by targeting phox2a and is regulated by HOTAIR. American Journal of Cancer Research, 6(2), 173–186.
- Wang, Y., Zhang, X., Wang, Z., Hu, Q., Wu, J., Li, Y., … Cheng, B. (2018). LncRNA-p23154 promotes the invasion-metastasis potential of oral squamous cell carcinoma by regulating Glut1-mediated glycolysis. Cancer Letters, 434, 172–183. https://doi.org/10.1016/j.canlet.2018.07.016
- Warnakulasuriya, S. (2009). Global epidemiology of oral and oropharyngeal cancer. Oral Oncology, 45(4–5), 309–316. https://doi.org/10.1016/j.oraloncology.2008.06.002
- Wei, L.-Q., Li, L., Lu, C., Liu, J., Chen, Y., & Wu, H. (2019). Involvement of H19/miR-326 axis in hepatocellular carcinoma development through modulating TWIST1. Journal of Cellular Physiology, 234(4), 5153–5162. https://doi.org/10.1002/jcp.27319
- Wu, K., Jiang, Y., Zhou, W., Zhang, B., Li, Y., Xie, F., … Cao, W. (2020). Long noncoding RNA RC3H2 facilitates cell proliferation and invasion by targeting microRNA-101-3p/EZH2 axis in OSCC. Molecular Therapy. Nucleic Acids, 20, 97–110. https://doi.org/10.1016/j.omtn.2020.02.006
- Xia, L., Nie, D., Wang, G., Sun, C., & Chen, G. (2019). FER1L4/miR-372/E2F1 works as a ceRNA system to regulate the proliferation and cell cycle of glioma cells. Journal of Cellular and Molecular Medicine, 23(5), 3224–3233. https://doi.org/10.1111/jcmm.14198
- Yang, Y. T., Wang, Y. F., Lai, J. Y., Shen, S. Y., Wang, F., Kong, J., … Yang, H. Y. (2016). Long non-coding RNA UCA1 contributes to the progression of oral squamous cell carcinoma by regulating the WNT/beta-catenin signaling pathway. Cancer Science, 107(11), 1581–1589. https://doi.org/10.1111/cas.13058
- Zhang, L., Meng, X., Zhu, X.-W., Yang, D.-C., Chen, R., Jiang, Y., & Xu, T. (2019). Long non-coding RNAs in Oral squamous cell carcinoma: Biologic function, mechanisms and clinical implications. Molecular Cancer, 18(1), 102. https://doi.org/10.1186/s12943-019-1021-3
- Zhao, G., Wang, S., Liang, X., Wang, C., & Peng, B. (2019). Oncogenic role of long non-coding RNA SNHG12 in gastric cancer cells by targeting miR-16. Experimental and Therapeutic Medicine, 18(1), 199–208. https://doi.org/10.3892/etm.2019.7526