Investigation of Tumor Suppressor miR-383 Expression in HPV-related Malignancies

Nilgün Çekin

doi:10.17776/csj.1882570

Investigation of Tumor Suppressor miR-383 Expression in HPV-related Malignancies

Abstract

Although genetic changes were investigated in disease development previously, we now know that epigenetic changes also play a critical role in diseases. In addition to DNA methylation and histone modification, changes in non-coding RNA expression also contribute to pathological processes as epigenetic modulators. miRNAs are conserved molecules that bind complementarily to their encoded target mRNAs, thereby performing post-transcriptional regulation. MicroRNA-383 (miR-383) functions as a tumor suppressor in various cancers, but its expression pattern in HPV-associated cervical lesions remains unclear. This exploratory study aimed to investigate whether miR-383 expression is altered in HPV‑positive cervical tissues and to generate hypotheses for future mechanistic studies. In this study, miR-383 expression levels were analyzed using qRT-PCR in paired HPV-positive cervical tissue and adjacent normal tissue samples from 30 patients. Our preliminary findings suggest a potential trend toward miR-383 upregulation, warranting further validation in larger cohorts. The observed upregulation may reflect a compensatory host response against viral oncogenesis, potentially through miR-383‑mediated repression of oncogenic targets such as SFN and PD‑L1, suggesting its role in restraining early cervical carcinogenesis and highlighting its potential as a biomarker in HPV‑related disease progression.

Keywords

Ethical Statement

Ethics committee approval was obtained for the samples of patient to be used in the study (file number: 2019-10/01)

Thanks

Thanks to for sample supply to Dr. İrem Küçükyıldız and Aslıhan Esra Bildirici. For your support, thanks to Şeyda Akın

References

Kombe Kombe, A. J., Li, B., Zahid, A., Mengist, H. M., Bounda, G. A., Zhou, Y., & Jin, T. (2020). Epidemiology and burden of Human Papillomavirus and related diseases, molecular pathogenesis, and vaccine evaluation. Frontiers in Public Health, 8, Article 552028. https://doi.org/10.3389/fpubh.2020.552028
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA: A Cancer Journal for Clinicians, 68(6), 394–424. https://doi.org/10.3322/caac.21492
Khoshnazar, M., Hosseini, S. M., Pashangzadeh, S., & Ghorat, F. (2025). Molecular interaction of human papilloma virus (HPV) with microRNAs: Insights into the development of cervical cancer and treatment approaches. Infectious Agents and Cancer, 20, Article 49. https://doi.org/10.1186/s13027-025-00677-9
Jafarzadeh, M., Soltani, B. M., & Mowla, S. J. (2022). MicroRNA-383: A tumor suppressor miRNA in human cancer. Frontiers in Cell and Developmental Biology, 10, Article 955486. https://doi.org/10.3389/fcell.2022.955486
Bartel, D. P. (2004). MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell, 116(2), 281–297. https://doi.org/10.1016/s0092-8674(04)00045-5
Bumrungthai, S., Ekalaksananan, T., Pientong, C., Promthet, S., & Patarapadungkit, N. (2015). Up-regulation of miR-21 is associated with cervicitis and human papillomavirus infection in cervical tissues. PLOS ONE, 10(5), e0127109. https://doi.org/10.1371/journal.pone.0127109
Asangani, I. A., Rasheed, S. A. K., Nikolova, D. A., Leupold, J. H., Post, S., & Allgayer, H. (2008). MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene, 27(15), 2128–2136. https://doi.org/10.1038/sj.onc.1210856
Babion, I., Mihelčić, M., Eijk, P. P., Steenbergen, R. D. M., Wilting, S. M., & de Menezes, R. X. (2020). miR-9-5p exerts a dual role in cervical cancer and targets transcription factor TWIST1. Cells, 9(1), 65. https://doi.org/10.3390/cells9010065

Wang, X., Wang, H. K., McCoy, J. P., Banerjee, N. S., Rader, J. S., Broker, T. R., ... & Zheng, Z. M. (2009). Oncogenic HPV infection interrupts the expression of tumor-suppressive miR-34a through viral oncoprotein E6. RNA, 15(4), 637–647. https://doi.org/10.1261/rna.1442309
Li, B., Lu, W., Yang, Q., Ge, Z., & Xie, X. (2020). WNT1, a target of miR-34a, promotes cervical squamous cell carcinoma proliferation and invasion by induction of an E-P cadherin switch via the WNT/β-catenin pathway. Cellular Oncology, 43(3), 489–503. https://doi.org/10.1007/s13402-020-00506-8
Nan, P., Guo, L., Cai, E., Li, H., & Zhou, Z. (2019). MiR-29a function as tumor suppressor in cervical cancer by targeting SIRT1 and predict patient prognosis. OncoTargets and Therapy, 12, 6917–6925. https://doi.org/10.2147/OTT.S218043
Yamamoto, N., Nohata, N., Fuse, M., Itesako, T., Yoshino, H., Enokida, H., ... & Seki, N. (2013). Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma. International Journal of Oncology, 43(6), 1855–1863. https://doi.org/10.3892/ijo.2013.2145
Saliminejad, K., Khorshid, H. R. K., & Ghaffari, S. H. (2019). Why have microRNA biomarkers not been translated from bench to clinic? Future Oncology, 15(8), 801–803. https://doi.org/10.2217/fon-2018-0812
Segal, M., & Slack, F. J. (2020). Challenges identifying efficacious miRNA therapeutics for cancer. Expert Opinion on Drug Discovery, 15(8), 987–991. https://doi.org/10.1080/17460441.2020.1765770
Hu, X., Schwarz, J. K., Lewis Jr, J. S., Huettner, P. C., Rader, J. S., Deasy, J. O., Grigsby, P. W., & Wang, X. (2010). A microRNA expression signature for cervical cancer prognosis. Cancer Research, 70(4), 1441–1448. https://doi.org/10.1158/0008-5472.CAN-09-3288
Wentzensen, N., Nason, M., Schiffman, M., Hunt, W. C., Rodriguez, A. C., Katki, H. A., ... & Wheeler, C. M. (2014). No evidence for synergy between human papillomavirus genotypes for the risk of high-grade squamous intraepithelial lesions in a large population-based study. The Journal of Infectious Diseases, 209(6), 855–864. https://doi.org/10.1093/infdis/jit577
Li, B., Hu, Y., Ye, F., Li, Y., Lv, W., & Xie, X. (2010). Reduced miR-34a expression in normal cervical tissues and cervical lesions with high-risk human papillomavirus infection. International Journal of Gynecological Cancer, 20(4), 597–604. https://doi.org/10.1111/j.1525-1438.2010.01573.x
Wang, X., Meyers, C., Guo, M., & Zheng, Z. M. (2011). Upregulation of p18Ink4c expression by oncogenic HPV E6 via p53-miR-34a pathway. International Journal of Cancer, 129(6), 1362–1372. https://doi.org/10.1002/ijc.25800
Martinez, I., Gardiner, A. S., Board, K. F., Monzon, F. A., Edwards, R. P., & Khan, S. A. (2008). Human papillomavirus type 16 reduces the expression of microRNA-218 in cervical carcinoma cells. Oncogene, 27(18), 2575–2582. https://doi.org/10.1038/sj.onc.1210919
Li, B. H., Zhou, J. S., Ye, F., Cheng, X. D., Zhou, C. Y., Lu, W. G., & Xie, X. (2011). Reduced miR-100 expression in cervical cancer and precursors and its carcinogenic effect through targeting PLK1 protein. European Journal of Cancer, 47(14), 2166–2174. https://doi.org/10.1016/j.ejca.2011.04.023
Lee, J. W., Choi, C. H., Choi, J. J., Park, Y. A., Kim, S. J., Hwang, S. Y., ... & Kim, B. G. (2008). Altered microRNA expression in cervical carcinomas. Clinical Cancer Research, 14(9), 2535–2542. https://doi.org/10.1158/1078-0432.CCR-07-1231
Hu, M., Dong, Z., Yang, J., & Cheng, Z. (2019). LINC01128 expedites cervical cancer progression by regulating miR-383-5p/SFN axis. BMC Cancer, 19, Article 1157. https://doi.org/10.1186/s12885-019-6326-5
Dong, P., Xiong, Y., Yue, J., Hanley, S. J. B., & Watari, H. (2018). Control of PD-L1 expression by miR-140/142/340/383 and oncogenic activation of the OCT4–miR-18a pathway in cervical cancer. Oncogene, 37(39), 5257–5268. https://doi.org/10.1038/s41388-018-0347-4

Details

Primary Language

English

Subjects

Cancer Biology

Journal Section

Research Article

Authors

Nilgün Çekin ^*
0000-0002-1000-7842
Türkiye

Publication Date

April 29, 2026

Submission Date

February 5, 2026

Acceptance Date

April 14, 2026

Published in Issue

Year 2026 Volume: 47 Number: 2

DOI

https://doi.org/10.17776/csj.1882570

IZ

https://izlik.org/JA76EP29FT

Cite

RIS / Bibtex

APA

Çekin, N. (2026). Investigation of Tumor Suppressor miR-383 Expression in HPV-related Malignancies. Cumhuriyet Science Journal, 47(2), 251-257. https://doi.org/10.17776/csj.1882570