https://doi.org/10.4081/ejh.2021.3295
miR-29a-3p enhances the radiosensitivity of oral squamous cell carcinoma cells by inhibiting ADAM12
Submitted: 24 June 2021
Accepted: 19 August 2021
Published: 27 September 2021
Accepted: 19 August 2021
Abstract Views: 864
PDF: 561
HTML: 17
HTML: 17
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the head and neck, and radiotherapy is the main approach for this disease, while irradiation resistance is a huge challenge that influences radiosensitivity. This study aims to determine the role and function of miR-29a-3p and ADAM12 in the radiosensitivity of OSCC cells. The expression pattern of ADAM12 in OSCC cells was searched in TCGA database. The binding of miR-29a-3p and ADAM12 was predicted by Starbase and verified using dual luciferase reporter gene assay. The RNA or protein expressions of miR-29a-3p and ADAM12 were measured by RT-qPCR or western blot. OSCC cell lines were treated by various γ-ray irradiation dosages before the alteration on miR-29a-3p expression and on the cell viability, proliferation, migration and cell apoptosis was detected. ADAM12 was highly expressed in OSCC cells, whose expression in resistant cells was positively correlated with irradiation dosage. Overexpression of ADAM12 in OSCC cells lead to increased cell proliferation and migration ability as well as inhibited cell apoptosis. miRNAs potentially binding ADAM12 in PITA, microT, miRmap and targetscan were screened, among which miR-29a-3p had the maximum differential expression levels in OSCC cells determined by RT-qPCR. Overexpression of miR-29a-3p resulted in suppressed cell viability, proliferation, migration ability and increased cell apoptosis, while this expression pattern can be partially counteracted by ADAM12 overexpression in OSCC cells. miR-29a-3p through targeting and inhibiting AMDM12 enhances the radiosensitivity of OSCC cells.
Wang J, Wang Y, Kong F, Han R, Song W, Chen D, et al. Identification of a six-gene prognostic signature for oral squamous cell carcinoma. J Cell Physiol 2020;235:3056-68.
DOI: https://doi.org/10.1002/jcp.29210
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86.
DOI: https://doi.org/10.1002/ijc.29210
Peng QS, Cheng YN, Zhang WB, Fan H, Mao QH, Xu P. circRNA_0000140 suppresses oral squamous cell carcinoma growth and metastasis by targeting miR-31 to inhibit Hippo signaling pathway. Cell Death Dis 2020;11:112.
DOI: https://doi.org/10.1038/s41419-020-2273-y
J SH, Hysi D. Methods and risk of bias in molecular marker prognosis studies in oral squamous cell carcinoma. Oral Dis 2018;24:115-9.
DOI: https://doi.org/10.1111/odi.12753
Matsuura D, Valim TD, Kulcsar MAV, Pinto FR, Brandao LG, Cernea CR, et al. Risk factors for salvage surgery failure in oral cavity squamous cell carcinoma. Laryngoscope 2018;128:1113-9.
DOI: https://doi.org/10.1002/lary.26935
Sharma A, Boaz K, Natarajan S. Understanding patterns of invasion: a novel approach to assessment of podoplanin expression in the prediction of lymph node metastasis in oral squamous cell carcinoma. Histopathology 2018;72:672-8.
DOI: https://doi.org/10.1111/his.13416
Song JM, Woo BH, Lee JH, Yoon S, Cho Y, Kim YD, et al. Oral administration of Porphyromonas gingivalis, a major pathogen of chronic periodontitis, promotes resistance to paclitaxel in mouse xenografts of oral squamous cell carcinoma. Int J Mol Sci 2019;20;2494.
DOI: https://doi.org/10.3390/ijms20102494
Fridman E, Na'ara S, Agarwal J, Amit M, Bachar G, Villaret AB, et al. The role of adjuvant treatment in early-stage oral cavity squamous cell carcinoma: An international collaborative study. Cancer 2018;124:2948-55.
DOI: https://doi.org/10.1002/cncr.31531
Yao C, Chang EI, Lai SY. Contemporary approach to locally advanced oral cavity squamous cell carcinoma. Curr Oncol Rep 2019;21:99.
DOI: https://doi.org/10.1007/s11912-019-0845-8
Lindemann A, Takahashi H, Patel AA, Osman AA, Myers JN. Targeting the DNA damage response in OSCC with TP53 mutations. J Dent Res 2018;97:635-644.
DOI: https://doi.org/10.1177/0022034518759068
Feng X, Luo Q, Zhang H, Wang H, Chen W, Meng G, et al. The role of NLRP3 inflammasome in 5-fluorouracil resistance of oral squamous cell carcinoma. J Exp Clin Cancer Res 2017;36:81.
DOI: https://doi.org/10.1186/s13046-017-0553-x
Yokota T, Homma A, Kiyota N, Tahara M, Hanai N, Asakage T, et al. Immunotherapy for squamous cell carcinoma of the head and neck. Jpn J Clin Oncol 2020;50:1089-96.
DOI: https://doi.org/10.1093/jjco/hyaa139
Veenstra VL, Damhofer H, Waasdorp C, van Rijssen LB, van de Vijver MJ, Dijk F, et al. ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy. Oncogenesis 2018;7:87.
DOI: https://doi.org/10.1038/s41389-018-0096-9
Markowski J, Tyszkiewicz T, Jarzab M, Oczko-Wojciechowska M, Gierek T, Witkowska M, et al. Metal-proteinase ADAM12, kinesin 14 and checkpoint suppressor 1 as new molecular markers of laryngeal carcinoma. Eur Arch Otorhinolaryngol 2009;266:1501-7.
DOI: https://doi.org/10.1007/s00405-009-1019-3
Ebbing EA, van der Zalm AP, Steins A, Creemers A, Hermsen S, Rentenaar R, et al. Stromal-derived interleukin 6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma. Proc Natl Acad Sci USA 2019;116:2237-42.
DOI: https://doi.org/10.1073/pnas.1820459116
Uehara E, Shiiba M, Shinozuka K, Saito K, Kouzu Y, Koike H, et al. Upregulated expression of ADAM12 is associated with progression of oral squamous cell carcinoma. Int J Oncol 2012;40:1414-22.
DOI: https://doi.org/10.3892/ijo.2012.1339
Pei Y, Yao Q, Li Y, Zhang X, Xie B. microRNA-211 regulates cell proliferation, apoptosis and migration/invasion in human osteosarcoma via targeting EZRIN. Cell Mol Biol Lett 2019;24:48.
DOI: https://doi.org/10.1186/s11658-019-0173-x
Aali M, Mesgarzadeh AH, Najjary S, Abdolahi HM, Kojabad AB, Baradaran B. Evaluating the role of microRNAs alterations in oral squamous cell carcinoma. Gene 2020;757:144936.
DOI: https://doi.org/10.1016/j.gene.2020.144936
Cai J, Qiao B, Gao N, Lin N, He W. Oral squamous cell carcinoma-derived exosomes promote M2 subtype macrophage polarization mediated by exosome-enclosed miR-29a-3p. Am J Physiol Cell Physiol 2019;316:C731-40.
DOI: https://doi.org/10.1152/ajpcell.00366.2018
Guo Y, Zhai J, Zhang J, Ni C, Zhou H. Improved radiotherapy sensitivity of nasopharyngeal carcinoma cells by miR-29-3p targeting COL1A1 3'-UTR. Med Sci Monit 2019;25:3161-9.
DOI: https://doi.org/10.12659/MSM.915624
Dinh TK, Fendler W, Chalubinska-Fendler J, Acharya SS, O'Leary C, Deraska PV, et al. Circulating miR-29a and miR-150 correlate with delivered dose during thoracic radiation therapy for non-small cell lung cancer. Radiat Oncol 2016;11:61.
DOI: https://doi.org/10.1186/s13014-016-0636-4
Burja B, Kuret T, Janko T, Topalovic D, Zivkovic L, Mrak-Poljsak K, et al. Olive leaf extract attenuates inflammatory activation and DNA damage in human arterial endothelial cells. Front Cardiovasc Med 2019;6:56.
DOI: https://doi.org/10.3389/fcvm.2019.00056
Roy R, Dagher A, Butterfield C, Moses MA. ADAM12 is a novel regulator of tumor angiogenesis via STAT3 signaling. Mol Cancer Res 2017;15:1608-1622.
DOI: https://doi.org/10.1158/1541-7786.MCR-17-0188
Luo ML, Zhou Z, Sun L, Yu L, Sun L, Liu J, et al. An ADAM12 and FAK positive feedback loop amplifies the interaction signal of tumor cells with extracellular matrix to promote esophageal cancer metastasis. Cancer Lett 2018;422:118-28.
DOI: https://doi.org/10.1016/j.canlet.2018.02.031
Wang X, Wang Y, Gu J, Zhou D, He Z, Wang X, et al. ADAM12-L confers acquired 5-fluorouracil resistance in breast cancer cells. Sci Rep 2017;7:9687.
DOI: https://doi.org/10.1038/s41598-017-10468-x
Duhachek-Muggy S, Qi Y, Wise R, Alyahya L, Li H, Hodge J, et al. Metalloprotease-disintegrin ADAM12 actively promotes the stem cell-like phenotype in claudin-low breast cancer. Mol Cancer 2017;16:32.
DOI: https://doi.org/10.1186/s12943-017-0599-6
Duhachek-Muggy S, Zolkiewska A. ADAM12-L is a direct target of the miR-29 and miR-200 families in breast cancer. BMC Cancer 2015;15:93.
DOI: https://doi.org/10.1186/s12885-015-1108-1
Wang JY, Zhang Q, Wang DD, Yan W, Sha HH, Zhao JH, et al. MiR-29a: a potential therapeutic target and promising biomarker in tumors. Biosci Rep 2018;38:BSR20171265.
DOI: https://doi.org/10.1042/BSR20171265
Huang C, Wang L, Song H, Wu C. MiR-29a inhibits the progression of oral squamous cell carcinoma by targeting Wnt/beta-catenin signalling pathway. Artif Cells Nanomed Biotechnol 2019;47:3037-42.
DOI: https://doi.org/10.1080/21691401.2019.1576712
Gao J, Shao Z, Yan M, Fu T, Zhang L, Yan Y. Targeted regulation of STAT3 by miR-29a in mediating Taxol resistance of nasopharyngeal carcinoma cell line CNE-1. Cancer Biomark 2018;22:641-8.
DOI: https://doi.org/10.3233/CBM-170964
Yang L, Li N, Yan Z, Li C, Zhao Z. MiR-29a-mediated CD133 expression contributes to cisplatin resistance in CD133(+) glioblastoma stem cells. J Mol Neurosci 2018;66:369-77.
DOI: https://doi.org/10.1007/s12031-018-1177-0
Yuan LL, Li L, Liu JN, Mei J, Lei CJ. Down-regulation of miR-29a facilitates apoptosis of colorectal carcinoma cell SW480 and suppresses its Paclitaxel resistance. Eur Rev Med Pharmacol Sci 2018;22:5499-507.
Shi X, Valizadeh A, Mir SM, Asemi Z, Karimian A, Majidina M, et al. miRNA-29a reverses P-glycoprotein-mediated drug resistance and inhibits proliferation via up-regulation of PTEN in colon cancer cells. Eur J Pharmacol 2020;880:173138.
DOI: https://doi.org/10.1016/j.ejphar.2020.173138
How to Cite
Jiang, C., Liu , F. ., Xiao, S. ., He, L. ., Wu, W. ., & Zhao, Q. . (2021). miR-29a-3p enhances the radiosensitivity of oral squamous cell carcinoma cells by inhibiting ADAM12. European Journal of Histochemistry, 65(3). https://doi.org/10.4081/ejh.2021.3295
Copyright (c) 2021 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- S.A. Ferreira, J.L.A. Vasconcelos, R.C.W.C. Silva, C.L.B. Cavalcanti, C.L. Bezerra, M.J.B.M. Rêgo, E.I.C. Beltrão, Expression patterns of α2,3-Sialyltransferase I and α2,6-Sialyltransferase I in human cutaneous epithelial lesions , European Journal of Histochemistry: Vol. 57 No. 1 (2013)
- S. Soddu, E. Di Felice, S. Cabras, M.E. Castellanos, L. Atzori, G. Faa, L. Pilloni, IMP-3 expression in keratoacanthomas and squamous cell carcinomas of the skin: an immunohistochemical study , European Journal of Histochemistry: Vol. 57 No. 1 (2013)
- Ying Wang, Shifa Yuan, Jing Ma, Hong Liu, Lizhen Huang, Fengzhen Zhang, Substance P is overexpressed in cervical squamous cell carcinoma and promoted proliferation and invasion of cervical cancer cells in vitro , European Journal of Histochemistry: Vol. 67 No. 3 (2023)
- A. Makowiecka, A. Simiczyjew, D. Nowak, A.J. Mazur, Varying effects of EGF, HGF and TGFβ on formation of invadopodia and invasiveness of melanoma cell lines of different origin , European Journal of Histochemistry: Vol. 60 No. 4 (2016)
- ChenHui Zhu, LiJuan Lin, ChangQing Huang, ZhiHui Wu, Activation of Hedgehog pathway by circEEF2/miR-625-5p/TRPM2 axis promotes prostate cancer cell proliferation through mitochondrial stress , European Journal of Histochemistry: Vol. 68 No. 4 (2024)
- T. Al-dhohorah, M. Mashrah, Z. Yao, J. Huang, Aberrant DKK3 expression in the oral leukoplakia and oral submucous fibrosis: a comparative immunohistochemical study , European Journal of Histochemistry: Vol. 60 No. 2 (2016)
- Azzurra Margiotta, Cinzia Progida, Oddmund Bakke, Cecilia Bucci, Characterization of the role of RILP in cell migration , European Journal of Histochemistry: Vol. 61 No. 2 (2017)
- C. Cui, P. Lal, S. Master, Y. Ma, T. Baradet, Z. Bing, Expression of parafibromin in major renal cell tumors , European Journal of Histochemistry: Vol. 56 No. 4 (2012)
- Renata Tabola, Magdalena Zaremba-Czogalla, Dagmara Baczynska, Roberto Cirocchi, Kamila Stach, Krzysztof Grabowski, Katarzyna Augoff, Fibroblast activating protein-α expression in squamous cell carcinoma of the esophagus in primary and irradiated tumors: the use of archival FFPE material for molecular techniques , European Journal of Histochemistry: Vol. 61 No. 2 (2017)
- Wei Wang, Wenbo Tang, Erbo Shan, Lei Zhang, Shiyuan Chen, Chaowen Yu, Yong Gao, MiR-130a-5p contributed to the progression of endothelial cell injury by regulating FAS , European Journal of Histochemistry: Vol. 66 No. 2 (2022)
You may also start an advanced similarity search for this article.
Publication Facts
Metric
This article
Other articles
Peer reviewers
2
2.4
Reviewer profiles N/A
Author statements
Author statements
This article
Other articles
Data availability
N/A
16%
External funding
N/A
32%
Competing interests
N/A
11%
Metric
This journal
Other journals
Articles accepted
57%
33%
Days to publication
94
145
- Editor & editorial board
- profiles
- Academic society
- N/A
- Publisher
- PAGEPress Publications, Pavia, Italy
To learn about these publication facts, click 
PF is maintained by the Public Knowledge Project
