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MMP1 3′UTR facilitates the proliferation and migration of human oral squamous cell carcinoma by sponging miR-188-5p to up-regulate SOX4 and CDK4

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Abstract

Growing evidence indicates that the non-coding 3′-untranslated region (3′UTR) of genes acts as competing endogenous RNAs (ceRNAs) to exert their roles in a number of diseases, including cancer. In the present study, MMP1 messenger RNA was identified to be significantly up-regulated in oral squamous cell carcinoma (OSCC) tissues, and both MMP1 and its 3′UTR promoted tumor growth and cell motility. Further mechanism investigations indicated that MMP1 3′UTR was able to antagonize miR-188-5p; in addition, overexpression of MMP1 3′UTR up-regulated the expression level of SOX4 and CDK4, target genes of miR-188-5p, which have also been identified as oncogenic driver genes in OSCC. Therefore, a ceRNA regulatory network among MMP1, SOX4, and CDK4 mediated via competing for binding to miR-188-5p was proved. Taken together, the present study demonstrates for the first time that MMP1 mRNA participates in the development of OSCC via ceRNA regulatory mechanism and genes involved in the ceRNA network may provide a novel avenue for target therapy.

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Availability of data and materials

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

This study was supported by Joint Funds for the innovation of Science and Technology, Fujian province (Grant Number: 2018Y9012).

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China

    Chengyong Wang, Chuanqing Mao, Yongzhen Lai, Zhiyu Cai & Weihui Chen

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  1. Chengyong Wang
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  2. Chuanqing Mao
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  3. Yongzhen Lai
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Contributions

CW and WC contributed to design this study. CW, CM, YL, and ZC conducted this study and were responsible for analysis and interpretation of the data. CW and WC contributed to manuscript drafting. WC revised the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Weihui Chen.

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The study was approved by the Ethics Committee of Fujian Medical University Union Hospital (Fuzhou, China; Approval No. 2019KJTYL037).

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Supplementary file1 (TIF 3384 kb)

Supplementary Figure S1. MMP1 is the target gene of miR-9-5p. A, The expression of miR-9-5p was examined in 10 pairs of OSCC tissues and the matched adjacent normal tissues by qRT-PCR. B, The relative luciferase activity was detected in the 293T cells that co-transfected with luciferase reporter constructs containing MMP1 3′UTR and miR-9-5p mimics. C, Detection of miR-9-5p using qRT-PCR in the Tca8113 cells stably expressing MMP1 3′UTR, stable cell lines containing empty vector were used as control. All values are represented as means ± SEM of the indicated number of measurements. Statistical analysis was conducted using Student t-test. *p<0.05, **p<0.01, ***p<0.001.

Supplementary file2 (TIF 6581 kb)

Supplementary Table S1. The primer sequences used for qRT-PCR.

Supplementary file3 (TIF 4664 kb)

Supplementary Table S2. Differentially expressed miRNAs identified in OSCC.

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Wang, C., Mao, C., Lai, Y. et al. MMP1 3′UTR facilitates the proliferation and migration of human oral squamous cell carcinoma by sponging miR-188-5p to up-regulate SOX4 and CDK4. Mol Cell Biochem 476, 785–796 (2021). https://doi.org/10.1007/s11010-020-03944-y

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