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Upregulation of MicroRNA-937 Predicts a Poor Prognosis and Promotes Hepatocellular Carcinoma Cell Proliferation, Migration, and Invasion

Abstract

Hepatocellular carcinoma (HCC) has a high dead rate partly due to late diagnosis. This study aimed to investigate the prognostic value of miR-937 in HCC and its role in the HCC progression. HCC tissue and adjacent non-cancerous tissues (NCT) (n = 125) were detected about the expression level of miR-937 via real-time quantitative PCR. The relationship between miR-937 expression and each important clinical characteristic was evaluated. And the prognostic significance of miR-937 was assessed by Kaplan–Meier curve and Cox regression analysis. CCK-8 and Transwell assays were conducted to observe the effects of miR-937 on HCC cell proliferation, migration, and invasion. The miR-937 expression was upregulated in HCC tissues, as well as in HCC cell lines. The upregulation of miR-937 showed a significant association with lymph node metastasis and TNM stage. Upregulation of miR-937 predicted poor prognosis of HCC patients. Overexpression of miR-937 promoted HCC cell ability of proliferation, migration, and invasiveness, while knockdown of miR-937 inhibited these cellular behaviors. miR-937 expression was upregulated in HCC and may serve as a promising prognostic factor and treated target for HCC patients. miR-937 might exert a promoter role in HCC through accelerated tumor cell proliferation, migration, and invasion.

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References

  1. Forner, A., Reig, M., & Bruix, J. (2018). Hepatocellular carcinoma. Lancet (London, England)., 391(10127), 1301–1314.

    Article  Google Scholar 

  2. Hartke, J., Johnson, M., & Ghabril, M. (2017). The diagnosis and treatment of hepatocellular carcinoma. Seminars in Diagnostic Pathology, 34(2), 153–159.

    Article  Google Scholar 

  3. Grandhi, M. S., Kim, A. K., Ronnekleiv-Kelly, S. M., Kamel, I. R., Ghasebeh, M. A., & Pawlik, T. M. (2016). Hepatocellular carcinoma: From diagnosis to treatment. Surgical Oncology, 25(2), 74–85.

    Article  Google Scholar 

  4. Ren, Z., Ma, X., Duan, Z., & Chen, X. (2020). Diagnosis, therapy, and prognosis for hepatocellular carcinoma. Analytical Cellular Pathology (Amsterdam)., 2020, 8157406.

    PubMed Central  Google Scholar 

  5. Lu, T. X., & Rothenberg, M. E. (2018). MicroRNA. The Journal of Allergy and Clinical Immunology, 141(4), 1202–1207.

    CAS  Article  Google Scholar 

  6. Mohr, A. M., & Mott, J. L. (2015). Overview of microRNA biology. Seminars in Liver Disease, 35(1), 3–11.

    CAS  Article  Google Scholar 

  7. Ying, S. Y., Chang, D. C., & Lin, S. L. (2008). The microRNA (miRNA): Overview of the RNA genes that modulate gene function. Molecular Biotechnology, 38(3), 257–268.

    CAS  Article  Google Scholar 

  8. Li, X., Zeng, Z., Wang, J., Wu, Y., Chen, W., Zheng, L., et al. (2020). MicroRNA-9 and breast cancer. Biomedicine & Pharmacotherapy [Biomedecine & Pharmacotherapie], 122, 109687.

    CAS  Article  Google Scholar 

  9. Lopez-Pedrera, C., Barbarroja, N., Patiño-Trives, A. M., Luque-Tévar, M., Torres-Granados, C., Aguirre-Zamorano, M. A., et al. (2020). Role of microRNAs in the development of cardiovascular disease in systemic autoimmune disorders. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms21062012

    Article  PubMed  PubMed Central  Google Scholar 

  10. Chen, F., Li, X. F., Fu, D. S., Huang, J. G., & Yang, S. E. (2017). Clinical potential of miRNA-221 as a novel prognostic biomarker for hepatocellular carcinoma. Cancer Biomarkers: Section A of Disease Markers, 18(2), 209–214.

    CAS  Article  Google Scholar 

  11. Rashad, N. M., El-Shal, A. S., Shalaby, S. M., & Mohamed, S. Y. (2018). Serum miRNA-27a and miRNA-18b as potential predictive biomarkers of hepatitis C virus-associated hepatocellular carcinoma. Molecular and Cellular Biochemistry, 447(1–2), 125–136.

    CAS  Article  Google Scholar 

  12. Shi, J., Li, X., Hu, Y., Zhang, F., Lv, X., Zhang, X., et al. (2020). MiR-1203 is involved in hepatocellular carcinoma metastases and indicates a poor prognosis. Neoplasma, 67(2), 267–276.

    CAS  Article  Google Scholar 

  13. Shi, B., Zhang, X., Chao, L., Zheng, Y., Tan, Y., Wang, L., et al. (2018). Comprehensive analysis of key genes, microRNAs and long non-coding RNAs in hepatocellular carcinoma. FEBS Open Bio, 8(9), 1424–1436.

    CAS  Article  Google Scholar 

  14. Li, Z., Lou, Y., Tian, G., Wu, J., Lu, A., Chen, J., et al. (2019). Discovering master regulators in hepatocellular carcinoma: One novel MR, SEC14L2 inhibits cancer cells. Aging, 11(24), 12375–12411.

    CAS  Article  Google Scholar 

  15. Carvalho de Oliveira, J., Molinari Roberto, G., Baroni, M., Bezerra Salomão, K., Alejandra Pezuk, J., & Sol Brassesco, M. (2018). MiRNA dysregulation in childhood hematological cancer. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms19092688

    Article  PubMed  PubMed Central  Google Scholar 

  16. Harrandah, A. M., Mora, R. A., & Chan, E. K. L. (2018). Emerging microRNAs in cancer diagnosis, progression, and immune surveillance. Cancer Letters, 438, 126–132.

    CAS  Article  Google Scholar 

  17. Qadir, M. I., & Rizvi, S. Z. (2017). miRNA in hepatocellular carcinoma: pathogenesis and therapeutic approaches. Critical Reviews in Eukaryotic Gene Expression., 27(4), 355–361.

    Article  Google Scholar 

  18. Nagy, Á., Lánczky, A., Menyhárt, O., & Győrffy, B. (2018). Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Scientific Reports, 8(1), 9227.

    Article  Google Scholar 

  19. Li, S., Yao, J., Xie, M., Liu, Y., & Zheng, M. (2018). Exosomal miRNAs in hepatocellular carcinoma development and clinical responses. Journal of Hematology & Oncology., 11(1), 54.

    Article  Google Scholar 

  20. Li, D., Zhang, J., & Li, J. (2020). Role of miRNA sponges in hepatocellular carcinoma. Clinica Chimica Acta, 500, 10–9.

    CAS  Article  Google Scholar 

  21. Clark, T., Maximin, S., Meier, J., Pokharel, S., & Bhargava, P. (2015). Hepatocellular carcinoma: Review of epidemiology, screening, imaging diagnosis, response assessment, and treatment. Current Problems in Diagnostic Radiology, 44(6), 479–486.

    Article  Google Scholar 

  22. Nishikawa, H., Arimoto, A., Wakasa, T., Kita, R., Kimura, T., & Osaki, Y. (2013). Comparison of clinical characteristics and survival after surgery in patients with non-B and non-C hepatocellular carcinoma and hepatitis virus-related hepatocellular carcinoma. Journal of Cancer, 4(6), 502–513.

    Article  Google Scholar 

  23. Tietze, L., & Kessler, S. M. (2020). The good, the bad, the question-H19 in hepatocellular carcinoma. Cancers. https://doi.org/10.3390/cancers12051261

    Article  PubMed  PubMed Central  Google Scholar 

  24. Zhang, T. Q., Su, Q. Q., Huang, X. Y., Yao, J. G., Wang, C., Xia, Q., et al. (2018). Micro RNA-4651 serves as a potential biomarker for prognosis when selecting hepatocellular carcinoma patients for postoperative adjuvant transarterial chemoembolization therapy. Hepatology Communications, 2(10), 1259–1273.

    CAS  Article  Google Scholar 

  25. D’Anzeo, M., Faloppi, L., Scartozzi, M., Giampieri, R., Bianconi, M., Del Prete, M., et al. (2014). The role of micro-RNAs in hepatocellular carcinoma: From molecular biology to treatment. Molecules (Basel, Switzerland)., 19(5), 6393–6406.

    Article  Google Scholar 

  26. Liu, H., Ma, L., Wang, L., & Yang, Y. (2019). MicroRNA-937 is overexpressed and predicts poor prognosis in patients with colon cancer. Diagnostic pathology., 14(1), 136.

    CAS  Article  Google Scholar 

  27. Li, D., Zhong, J., Zhang, G., Lin, L., & Liu, Z. (2019). Oncogenic role and prognostic value of microRNA-937-3p in patients with breast cancer. OncoTargets and Therapy, 12, 11045–11056.

    CAS  Article  Google Scholar 

  28. Zhang, L., Zeng, D., Chen, Y., Li, N., Lv, Y., Li, Y., et al. (2016). miR-937 contributes to the lung cancer cell proliferation by targeting INPP4B. Life Sciences, 155, 110–115.

    CAS  Article  Google Scholar 

  29. Fujiwara, T., & Yada, T. (2013). miRNA-target prediction based on transcriptional regulation. BMC Genomics, 14(Suppl 2), S3.

    Article  Google Scholar 

  30. Zhou, D., Dong, L., Yang, L., Ma, Q., Liu, F., Li, Y., et al. (2020). Identification and analysis of circRNA-miRNA-mRNA regulatory network in hepatocellular carcinoma. IET Systems Biology, 14(6), 391–398.

    Article  Google Scholar 

  31. Eun, J. W., Seo, C. W., Baek, G. O., Yoon, M. G., Ahn, H. R., Son, J. A., et al. (2020). Circulating exosomal microRNA-1307-5p as a predictor for metastasis in patients with hepatocellular carcinoma. Cancers. https://doi.org/10.3390/cancers12123819

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We deeply thanks to the help from Jinyun Li and Yan Wang (Department of Pathology, The Second Affiliated Hospital of Kunming Medical University) for the tissue pathological confirmation.

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All authors initiated and designed the work, analyzed the data, and wrote and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Zhangbin Chen or Yu Zhang.

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The authors declare that they have no conflict of interest.

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The study was approved by the Ethics Committee of Affiliated Hospital of the Second Affiliated Hospital of Kunming Medical University.

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Chen, Z., Zhang, Y. Upregulation of MicroRNA-937 Predicts a Poor Prognosis and Promotes Hepatocellular Carcinoma Cell Proliferation, Migration, and Invasion. Mol Biotechnol 64, 33–41 (2022). https://doi.org/10.1007/s12033-021-00388-7

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  • DOI: https://doi.org/10.1007/s12033-021-00388-7

Keywords

  • miR-937
  • Hepatocellular carcinoma
  • Prognosis
  • Cellular behavior