Squamous cell carcinomas (SCCs) in the anogenital and head and neck regions are associated with high-risk types of human papillomaviruses (HR-HPV). Deregulation of miRNA expression is an important contributor to carcinogenesis. This study aimed to pinpoint commonly and uniquely deregulated miRNAs in cervical, anal, vulvar, and tonsillar tumors of viral or non-viral etiology, searching for a common set of deregulated miRNAs linked to HPV-induced carcinogenesis. RNA was extracted from tumors and nonmalignant tissues from the same locations. The miRNA expression level was determined by next-generation sequencing. Differential expression of miRNAs was calculated, and the patterns of miRNA deregulation were compared between tumors. The total of deregulated miRNAs varied between tumors of different locations by two orders of magnitude, ranging from 1 to 282. The deregulated miRNA pool was largely tumor-specific. In tumors of the same location, a low proportion of miRNAs were exclusively deregulated and no deregulated miRNA was shared by all four types of HPV-positive tumors. The most significant overlap of deregulated miRNAs was found between tumors which differed in location and HPV status (HPV-positive cervical tumors vs. HPV-negative vulvar tumors). Our results imply that HPV infection does not elicit a conserved miRNA deregulation in SCCs.

BIOCEV Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University 25250 Vestec Czech Republic

Department of Genetics and Microbiology Faculty of Science Charles University 12844 Prague Czech Republic

Genomics Core Facility EMBL 69117 Heidelberg Germany

Zobrazit více v PubMed

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Lu H.J., Jin P.Y., Tang Y., Fan S.H., Zhang Z.F., Wang F., Wu D.M., Lu J., Zheng Y.L. MicroRNA-136 inhibits proliferation and promotes apoptosis and radiosensitivity of cervical carcinoma through the NF-κB pathway by targeting E2F1. Life Sci. 2018;199:167–178. doi: 10.1016/j.lfs.2018.02.016. PubMed DOI

Zhang B.X., Yu T., Yu Z., Yang X.G. MicroRNA-148a regulates the MAPK/ERK signaling pathway and suppresses the development of esophagus squamous cell carcinoma via targeting MAP3K9. Eur. Rev. Med. Pharmacol. Sci. 2019;23:6497–6504. doi: 10.26355/eurrev_201908_18533. PubMed DOI

Jia T., Ren Y., Wang F., Zhao R., Qiao B., Xing L., Ou L., Guo B. MiR-148a inhibits oral squamous cell carcinoma progression through ERK/MAPK pathway via targeting IGF-IR. BioSci. Rep. 2020;40 doi: 10.1042/BSR20182458. PubMed DOI PMC

Mou Z., Xu X., Dong M., Xu J. MicroRNA-148b acts as a tumor suppressor in cervical cancer by inducing G1/S-phase cell cycle arrest and apoptosis in a caspase-3-dependent manner. Med. Sci. Monit. 2016;22:2809–2815. doi: 10.12659/MSM.896862. PubMed DOI PMC

Zhang H., Lu Y., Wang S., Sheng X., Zhang S. MicroRNA-152 acts as a tumor suppressor microRNA by inhibiting Krüppel-like factor 5 in human cervical cancer. Oncol. Res. 2019;27:335–340. doi: 10.3727/096504018X15252202178408. PubMed DOI PMC

Wang X., Li G.H. MicroRNA-16 functions as a tumor-suppressor gene in oral squamous cell carcinoma by targeting AKT3 and BCL2L2. J. Cell Physiol. 2018;233:9447–9457. doi: 10.1002/jcp.26833. PubMed DOI PMC

Wei Q., Li Y.X., Liu M., Li X., Tang H. MiR-17-5p targets TP53INP1 and regulates cell proliferation and apoptosis of cervical cancer cells. IUBMB Life. 2012;64:697–704. doi: 10.1002/iub.1051. PubMed DOI

Koshizuka K., Hanazawa T., Kikkawa N., Arai T., Okato A., Kurozumi A., Kato M., Katada K., Okamoto Y., Seki N. Regulation of ITGA3 by the anti-tumor miR-199 family inhibits cancer cell migration and invasion in head and neck cancer. Cancer Sci. 2017;108:1681–1692. doi: 10.1111/cas.13298. PubMed DOI PMC

Wei D., Shen B., Wang W., Zhou Y., Yang X., Lu G., Yang J., Shao Y. MicroRNA-199a-5p functions as a tumor suppressor in oral squamous cell carcinoma via targeting the IKKβ/NF-κB signaling pathway. Int. J. Mol. Med. 2019;43:1585–1596. doi: 10.3892/ijmm.2019.4083. PubMed DOI PMC

Wei D., Wang W., Shen B., Zhou Y., Yang X., Lu G., Yang J., Shao Y. MicroRNA-199a-5p suppresses migration and invasion in oral squamous cell carcinoma through inhibiting the EMT-related transcription factor SOX4. Int. J. Mol. Med. 2019;44:185–195. doi: 10.3892/ijmm.2019.4174. PubMed DOI PMC

Qu X., Gao D., Ren Q., Jiang X., Bai J., Sheng L. MiR-211 inhibits proliferation, invasion and migration of cervical cancer via targeting SPARC. Oncol. Lett. 2018;16:853–860. doi: 10.3892/ol.2018.8735. PubMed DOI PMC

Zhu L., Tu H., Liang Y., Tang D. MiR-218 produces anti-tumor effects on cervical cancer cells in vitro. World J. Surg. Oncol. 2018;16:204. doi: 10.1186/s12957-018-1506-3. PubMed DOI PMC

Liu C., Zhang Y., Liang S., Ying Y. Aldehyde dehydrogenase 1, a target of miR-222, is expressed at elevated levels in cervical cancer. Exp. Ther. Med. 2020;19:1673–1680. doi: 10.3892/etm.2020.8425. PubMed DOI PMC

Chen F., Qi S., Zhang X., Wu J., Yang X., Wang R. MiR-23a-3p suppresses cell proliferation in oral squamous cell carcinomas by targeting FGF2 and correlates with a better prognosis: miR-23a-3p inhibits OSCC growth by targeting FGF2. Pathol. Res. Pract. 2019;215:660–667. doi: 10.1016/j.prp.2018.12.021. PubMed DOI

Xu L., Chen Z., Xue F., Chen W., Ma R., Cheng S., Cui P. MicroRNA-24 inhibits growth, induces apoptosis, and reverses radioresistance in laryngeal squamous cell carcinoma by targeting X-linked inhibitor of apoptosis protein. Cancer Cell Int. 2015;15:61. doi: 10.1186/s12935-015-0217-x. PubMed DOI PMC

Guo Y., Fu W., Chen H., Shang C., Zhong M. MiR-24 functions as a tumor suppressor in Hep2 laryngeal carcinoma cells partly through down-regulation of the S100A8 protein. Oncol. Rep. 2012;27:1097–1103. doi: 10.3892/or.2011.1571. PubMed DOI PMC

Fang F., Huang B., Sun S., Xiao M., Guo J., Yi X., Cai J., Wang Z. MiR-27a inhibits cervical adenocarcinoma progression by downregulating the TGF-βRI signaling pathway. Cell Death Dis. 2018;9:395. doi: 10.1038/s41419-018-0431-2. PubMed DOI PMC

Han M., Li N., Li F., Wang H., Ma L. MiR-27b-3p exerts tumor suppressor effects in esophageal squamous cell carcinoma by targeting Nrf2. Hum. Cell. 2020;33:641–651. doi: 10.1007/s13577-020-00329-7. PubMed DOI

Xie R., Wu S.N., Gao C.C., Yang X.Z., Wang H.G., Zhang J.L., Yan W., Ma T.H. MicroRNA-30d inhibits the migration and invasion of human esophageal squamous cell carcinoma cells via the post-transcriptional regulation of enhancer of zeste homolog 2. Oncol. Rep. 2017;37:1682–1690. doi: 10.3892/or.2017.5405. PubMed DOI

Hu J., Gui Y., Xie P., Li G. MicroRNA-33a regulates the invasion of cervical cancer cells via targeting Twist1. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2015;40:1060–1067. doi: 10.11817/j.issn.1672-7347.2015.10.002. PubMed DOI

Deng Y., Xiong Y., Liu Y. MiR-376c inhibits cervical cancer cell proliferation and invasion by targeting BMI1. Int. J. Exp. Pathol. 2016;97:257–265. doi: 10.1111/iep.12177. PubMed DOI PMC

Shan D., Shang Y., Hu T. MicroRNA-411 inhibits cervical cancer progression by directly targeting STAT3. Oncol. Res. 2019;27:349–358. doi: 10.3727/096504018X15247361080118. PubMed DOI PMC

Xin J.X., Yue Z., Zhang S., Jiang Z.H., Wang P.Y., Li Y.J., Pang M., Xie S.Y. MiR-99 inhibits cervical carcinoma cell proliferation by targeting TRIB2. Oncol. Lett. 2013;6:1025–1030. doi: 10.3892/ol.2013.1473. PubMed DOI PMC

Wu T., Chen X., Peng R., Liu H., Yin P., Peng H., Zhou Y., Sun Y., Wen L., Yi H., et al. Let-7a suppresses cell proliferation via the TGF-β/SMAD signaling pathway in cervical cancer. Oncol. Rep. 2016;36:3275–3282. doi: 10.3892/or.2016.5160. PubMed DOI

Guo M., Zhao X., Yuan X., Jiang J., Li P. MiR-let-7a inhibits cell proliferation, migration, and invasion by down-regulating PKM2 in cervical cancer. Oncotarget. 2017;8:28226–28236. doi: 10.18632/oncotarget.15999. PubMed DOI PMC

Zheng S., Liu Q., Ma R., Tan D., Shen T., Zhang X., Lu X. Let-7b-5p inhibits proliferation and motility in squamous cell carcinoma cells through negative modulation of KIAA1377. Cell Biol. Int. 2019;43:634–641. doi: 10.1002/cbin.11136. PubMed DOI

Hou B., Ishinaga H., Midorikawa K., Nakamura S., Hiraku Y., Oikawa S., Ma N., Takeuchi K., Murata M. Let-7c inhibits migration and epithelial-mesenchymal transition in head and neck squamous cell carcinoma by targeting IGF1R and HMGA2. Oncotarget. 2018;9:8927–8940. doi: 10.18632/oncotarget.23826. PubMed DOI PMC

Zheng Y., Luo M., Lü M., Zhou T., Liu F., Guo X., Zhang J., Kang M. Let-7c-5p inhibits cell proliferation and migration and promotes apoptosis via the CTHRC1/AKT/ERK pathway in esophageal squamous cell carcinoma. Onco Targets Ther. 2020;13:11193–11209. doi: 10.2147/OTT.S274092. PubMed DOI PMC

Wang S., Jin S., Liu M.D., Pang P., Wu H., Qi Z.Z., Liu F.Y., Sun C.F. hsa-let-7e-5p inhibits the proliferation and metastasis of head and neck squamous cell carcinoma cells by targeting chemokine receptor 7. J. Cancer. 2019;10:1941–1948. doi: 10.7150/jca.29536. PubMed DOI PMC

Cheng Y., Guo Y., Zhang Y., You K., Li Z., Geng L. MicroRNA-106b is involved in transforming growth factor β1-induced cell migration by targeting disabled homolog 2 in cervical carcinoma. J. Exp. Clin. Cancer Res. 2016;35:11. doi: 10.1186/s13046-016-0290-6. PubMed DOI PMC

Wang M., Wang X., Liu W. MicroRNA-130a-3p promotes the proliferation and inhibits the apoptosis of cervical cancer cells via negative regulation of RUNX3. Mol. Med. Rep. 2020;22:2990–3000. doi: 10.3892/mmr.2020.11368. PubMed DOI

Li J.H., Zhang Z., Du M.Z., Guan Y.C., Yao J.N., Yu H.Y., Wang B.J., Wang X.L., Wu S.L., Li Z. MicroRNA-141-3p fosters the growth, invasion, and tumorigenesis of cervical cancer cells by targeting FOXA2. Arch. BioChem. Biophys. 2018;657:23–30. doi: 10.1016/j.abb.2018.09.008. PubMed DOI

Wang H., Hu H., Luo Z., Liu S., Wu W., Zhu M., Wang J., Liu Y., Lu Z. MiR-4454 up-regulated by HPV16 E6/E7 promotes invasion and migration by targeting ABHD2/NUDT21 in cervical cancer. BioSci. Rep. 2020;40 doi: 10.1042/BSR20200796. PubMed DOI PMC