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Exosomal miR-21-5p contributes to ovarian cancer progression by regulating CDK6

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Abstract

Ovarian cancer is a predominant gynecologic malignancy and correlated with high mortality and severe morbidity. Exosomal microRNAs (miRNAs) play crucial roles in various processes during the progression of ovarian cancer, such as cell proliferation, apoptosis, and invasion. However, the function of exosomal miR-21-5p in ovarian cancer is still unknown. Here, we found that miR-21-5p was upregulated in ovarian cancer tissues, plasma exosomes of ovarian cancer patients, and exosomes from ovarian cancer cells. MiR-21-5p was incorporated in the exosomes from the ovarian cancer cells. In addition, 5-ethynyl-2′-deoxyuridine (Edu), a marker of cancer cell proliferation, was enhanced by miR-21-5p mimic while reduced by miR-21-5p inhibitor in ovarian cancer cells. MiR-21-5p mimic could increase, but miR-21-5p inhibitor could decrease the migration and invasion of cancer cells. Ovarian cancer cell apoptosis was induced by miR-21-5p inhibitor. Moreover, miR-21-5p inhibitor could up-regulate the expression of pro-apoptotic cleaved caspase3 and Bax while downregulate the expression of anti-apoptotic Bcl2 in the cells. Exosomal miR-21-5p inhibited the expression of cyclin-dependent kinase 6 (CDK6) by targeting its 3′-untranslated region (3′-UTR) at both the mRNA and protein levels. Tumorigenicity analysis in nude mice revealed that exosomal miR-21-5p could increase tumor volume, size, and weight of ovarian cancer in vivo. Besides, miR-21-5p targeted CDK6 in tumor tissues of nude mice. In conclusion, exosomal miR-21-5p contributes to the progression of ovarian cancer by regulating CDK6. Our findings will provide novel insights into the mechanism of exosomal miR-21-5p in the development of ovarian cancer. Exosomal miR-21-5p may serve as a potential target for the therapy of ovarian cancer.

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Funding

This work was supported by 2018 Nanjing Health Science and Technology Development Project (Grant No. YKK18158) and 2019 Natural Science Research Project of Anhui Educational Committee (Grant No. KJ2019A0384).

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  1. Jian Cao and Yuan Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, No. 123 Tianfei Lane, Mochou Road, Nanjing City, Jiangsu Province, 210004, People’s Republic of China

    Jian Cao, Dazhen Yang & Xiaoyan Gu

  2. Department of Gynecology Oncology, The First Affiliated Hospital of Bengbu Medical College, No. 287 Changhuai Road, Bengbu City, Anhui Province, 233000, People’s Republic of China

    Yuan Zhang & Jing Zhang

  3. Department of Nutrition, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004, People’s Republic of China

    Juan Mu

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  1. Jian Cao
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  5. Xiaoyan Gu
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Correspondence to Xiaoyan Gu or Jing Zhang.

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The clinical samples used in this study under the written approval of the patients and healthy cases. This study conformed to the experimental guidelines of the World Medical Association and the Ethics Committee of The First Affiliated Hospital of Bengbu Medical College. Animal care and method procedure were authorized by the Animal Ethics Committee.

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Cao, J., Zhang, Y., Mu, J. et al. Exosomal miR-21-5p contributes to ovarian cancer progression by regulating CDK6. Human Cell 34, 1185–1196 (2021). https://doi.org/10.1007/s13577-021-00522-2

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