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miR-203a-3p-DNMT3B feedback loop facilitates non-small cell lung cancer progression

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Abstract

It has been reported that microRNA-203a-3p (miR-203a-3p) modulates cell proliferation, migration and invasion in a variety of cancer cell types. However, little is known about its role in lung cancer progression. The present study found that miR-203a-3p was downregulated in non-small cell lung cancer (NSCLC) cell lines and tissues. Overexpression of miR-203a-3p inhibits NSCLC cell proliferation, migration and invasion, and promotes cellular apoptosis in vitro. Restoration of miR-203a-3p expression in A549 and NCI-H520 cells enhances their chemosensitivity. Further experiments showed that DNA methyltransferase 3B (DNMT3B) was a direct target of miR-203a-3p. In addition, the present results revealed that promoter hypermethylation was the potential mechanism responsible for low miR-203a-3p expression in NSCLC. Notably, feedback regulation between miR-203a-3p and DNMT3B was observed in NSCLC. Moreover, Overexpression of miR-203a-3p reduces tumor growth in vivo. In summary, the present study has identified an miR-203a-3p-DNMT3B feedback loop that facilitates NSCLC progression.

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Funding

National Natural Science Foundation of China, 81772480, Songwang Cai, Natural Science Foundation of Guangdong Province, 2020A1515011437, Songwang Cai.

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Author notes

  1. Pingshan Yang, Dongdong Zhang and Fengli Zhou contributed equally to this work.

Authors and Affiliations

  1. Department of Thoracic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, Guangdong, People’s Republic of China

    Pingshan Yang, Dongdong Zhang, Wenyou Chen, Chuang Hu, Duqing Xiao & Songwang Cai

  2. Departments of General Practice, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, Guangdong, People’s Republic of China

    Fengli Zhou

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  1. Pingshan Yang
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  2. Dongdong Zhang
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  3. Fengli Zhou
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  5. Chuang Hu
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  6. Duqing Xiao
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  7. Songwang Cai
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Correspondence to Songwang Cai.

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The authors declared that they have no competing interests.

Ethical approval

The human study was approved by the institutional research ethics committee of The First Affiliated Hospital of Jinan University (No. KYk-2022-003). And the animal experiments was approved by the Institutional Animal Care and Use Committee of Jinan University (IACUC-20191130-01).

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Yang, P., Zhang, D., Zhou, F. et al. miR-203a-3p-DNMT3B feedback loop facilitates non-small cell lung cancer progression. Human Cell 35, 1219–1233 (2022). https://doi.org/10.1007/s13577-022-00728-y

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  • DOI: https://doi.org/10.1007/s13577-022-00728-y

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