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Dissecting the functional role of microRNA 21 in osteosarcoma

Cancer Gene Therapy volume 26, pages 179–182 (2019)Cite this article

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Abstract

Osteosarcoma (OS) is considered to be a malignant bone tumour that mainly affects the long bones, but it is also involved in other bones of the body. Currently, surgery and chemotherapy have achieved some response to patients with OS, but they are not increasing the survival rate as well as treatment options. Researchers made lot of drug options for OS, but yet, no treatment is existing in sight for the disease and needs a new insight into the molecular and signaling pathways for the disease. Now, it is necessary to develop a novel and alternative strategy for the prognosis, diagnosis and treatment options for OS. MicroRNAs (miRNAs) are a small non-coding RNA, and their size ranges from 18 to 22 nt in length. In the nucleus, miRNAs originate and transcribe into primary transcripts and later cleaved to produce stem loop-structured precursor nucleotides. microRNA 21 (miR-21) is considered to be a trivial marker for many diseases and has been upregulated in many cancers. Moreover, it plays a main role in proliferation, migration, invasion and apoptosis. miR-21 and its associated pathways are very important and play a critical role in the pathogenesis of OS and are considered to be a biomarker and a therapeutic target for OS. To our knowledge, there is no paper that demonstrates the responsibility and the role of miR-21 in OS and the number of studies related to miR-21 in OS is spare. Therefore, the main aim of this paper is to give an outline of the recent clinical investigation and importance of miR-21 in OS. It has been suggested that the up- and downregulation of miRNAs plays a crucial role in the pathogenesis and progression of OS. Normally, miR-21 was found to be upregulated in OS; however, we summarize the clinical relevance and the recent research findings associated with miR-21 in OS.

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References

  1. Moore DD, Luu HH. Osteosarcoma. Cancer Treat Res. 2014;162:65–92.

    Article  Google Scholar 

  2. Sampson VB, Yoo S, Kumar A, Vetter NS, Anders Kolb E. MicroRNAs and Potential Targets in Osteosarcoma: Review. Front Pediatr. 2015;3:69.

    Article  Google Scholar 

  3. Mohseny AB, Szuhai K, Romeo S, Buddingh EP, Briaire-de BI, de Jong D, et al. Osteosarcoma originates from mesenchymal stem cells in consequence of aneuploidization and genomic loss of Cdkn2. J Pathol. 2009;219:294–305.

    Article  CAS  Google Scholar 

  4. Cheng D, Qiu X, Zhuang M, Zhu C, Zou H, Liu Z. MicroRNAs with prognostic significance in osteosarcoma: a systemic review and meta-analysis. Oncotarget. 2017;8:81062–74.

    PubMed  PubMed Central  Google Scholar 

  5. D Sekar. Comment on the potential role of microRNAs in hypertension. J Hum Hypertens 2018;32:639.

    Article  Google Scholar 

  6. Panagal M, Biruntha M, Vidhyavathi RM, Sivagurunathan P, Senthilkumar SR, Sekar D. Dissecting the role of miR-21 in different types of stroke. Gene. 2019;681:69–72.

    Article  CAS  Google Scholar 

  7. Panagal M, S R SK PS, M B, M K, Gopinathe V, et al. MicroRNA21 and the various types of myeloid leukemia. Cancer Gene Ther. 2018;25:161–6.

    Article  CAS  Google Scholar 

  8. Priyanka P, Panagal M, Sivakumar P, Gopinath V, Ananthavalli R, Karthigeyan M, et al. Identification, expression, and methylation of miR-7110 and its involvement in type 1 diabetes mellitus. Gene Rep. 2018;11:229–34.

    Article  Google Scholar 

  9. Martin-Guerrero I, Bilbao-Aldaiturriaga N, Gutierrez-Camino A, Santos-Zorrozua B, Dolžan V, Patiño-Garcia A, et al. Variants in the 14q32 miRNA cluster are associated with osteosarcoma risk in the Spanish population. Sci Rep. 2018;8:15414.

    Article  Google Scholar 

  10. Sekar D, Venugopal B, Sekar P, Ramalingam K. Role of microRNA 21 in diabetes and associated/related diseases. Gene. 2016;582:14–8.

    Article  CAS  Google Scholar 

  11. Sekar D, Krishnan R, Panagal M, Sivakumar P, Gopinath V, Basam V. Deciphering the role of microRNA 21 in cancer stem cells (CSCs). Genes Dis. 2016;3:277–81.

    Article  CAS  Google Scholar 

  12. Shang G, Mi Y, Mei Y, Wang G, Wang Y, Li X, et al. MicroRNA-192 inhibits the proliferation, migration and invasion of osteosarcoma cells and promotes apoptosis by targeting matrix metalloproteinase-11. Oncol Lett. 2018;15:7265–72.

    PubMed  PubMed Central  Google Scholar 

  13. Pan X, Wang Z-X, Wang R. MicroRNA-21: a novel therapeutic target in human cancer. Cancer Biol Ther. 2010;10:1224–32.

    Article  CAS  Google Scholar 

  14. Ribas J, Ni X, Castanares M, Liu MM, Esopi D, Yegnasubramanian S, et al. A novel source for miR-21 expression through the alternative polyadenylation ofVMP1 gene transcripts. Nucleic Acids Res. 2012;40:6821–33.

    Article  CAS  Google Scholar 

  15. Sekar D, Hairul Islam VI, Thirugnanasambantham K, Saravanan S. Relevance of miR-21 in HIV and non-HIV-related lymphomas. Tumour Biol. 2014;35:8387–93.

    Article  CAS  Google Scholar 

  16. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133:647–58.

    Article  CAS  Google Scholar 

  17. Zhu S, Si ML, Wu H, Mo YY. MicroRNA-21 targets the tumor suppressor genetropomyosin1 (TPM1). J Biol Chem. 2007;282:14328–36.

    Article  CAS  Google Scholar 

  18. Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008;27:2128–36.

    Article  CAS  Google Scholar 

  19. Yu Y, Nangia-Makker P, Farhana L, Rajendra G, Levi S, Majumdar E. AP. miR-21 and miR-145 cooperation in regulation of colon cancer stem cells. Mol Cancer. 2015;14:98.

    Article  Google Scholar 

  20. Zhu KP, Zhang CL, Ma XL, Hu JP, Cai T, Zhang L. Analyzing the Interactions of mRNAs and ncRNAs to Predict Competing Endogenous RNA Networks in Osteosarcoma Chemo-Resistance. Mol Ther. 2019. pii: S1525-0016(19)30002-4.

  21. Heishima K, Meuten T, Yoshida K, Mori T, Thamm DH. Prognostic significance of circulating microRNA-214 and -126 in dogs with appendicular osteosarcoma receiving amputation and chemotherapy. BMC Vet Res. 2019;15:39.

    Article  Google Scholar 

  22. Shekhar R, Priyanka P, Kumar P, Ghosh T, Khan MM, Nagarajan P et al. The microRNAs miR-449a and miR-424 suppress osteosarcoma by targeting cyclin A2 expression. J Biol Chem. 2019. pii: jbc.RA118.005778.

  23. Zhao J, Zhang C, Gao Z, Wu H, Gu R, Jiang R. Long non-coding RNA ASBEL promotes osteosarcoma cell proliferation, migration, and invasion by regulating microRNA-21. J Cell Biochem. 2018;119:6461–9.

    Article  CAS  Google Scholar 

  24. Hua Y, Jin Z, Zhou F, Zhang YQ, Zhuang Y. The expression significance of serum MiR-21 in patients with osteosarcoma and its relationship with chemosensitivity. Eur Rev Med Pharmacol Sci. 2017;21:2989–94.

    CAS  PubMed  Google Scholar 

  25. Nakka M, Allen-Rhoades W, Li Y, Kelly AJ, Shen J, Taylor AM, et al. TARGET osteosarcoma consortium. Biomarker significance of plasma and tumor miR-21, miR-221, and miR-106a in osteosarcoma. Oncotarget. 2017;8:96738–52.

    Article  Google Scholar 

  26. Yuan J, Chen L, Chen X, Sun W, Zhou X. Identification of serum microRNA-21 as a biomarker for chemosensitivity and prognosis in human osteosarcoma. J Int Med Res. 2012;40:2090–7.

    Article  CAS  Google Scholar 

  27. Ziyan W, Yang L. MicroRNA-21 regulates the sensitivity to cisplatin in a human osteosarcoma cell line. Ir J Med Sci. 2016;185:85–91.

    Article  CAS  Google Scholar 

  28. Zhang R, Xia T. Long non-coding RNA XIST regulates PDCD4 expression by interacting with miR-21-5p and inhibits osteosarcoma cell growth and metastasis. Int J Oncol. 2017;51:1460–70.

    Article  CAS  Google Scholar 

  29. Yang C, Wang G, Yang J, Wang L. Long noncoding RNA NBAT1 negatively modulates growth and metastasis of osteosarcoma cells through suppression of miR-21. Am J Cancer Res. 2017;7:2009–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Heng L, Jia Z, Bai J, Zhang K, Zhu Y, Ma J, et al. Molecular characterization of metastatic osteosarcoma: differentially expressed genes, transcription factors and microRNAs. Mol Med Rep. 2017;15:2829–36.

    Article  CAS  Google Scholar 

  31. Xu B, Xia H, Cao J, Wang Z, Yang Y, Lin Y. MicroRNA-21 Inhibits the Apoptosis of Osteosarcoma Cell Line SAOS-2 via Targeting Caspase 8. Oncol Res. 2017;25:1161–8.

    Article  Google Scholar 

  32. Ren X, Shen Y, Zheng S, Liu J, Jiang X. miR-21 predicts poor prognosis in patients with osteosarcoma. Br J Biomed Sci. 2016;73:158–62.

    Article  Google Scholar 

  33. Lv C, Hao Y, Tu G. MicroRNA-21 promotes proliferation, invasion and suppresses apoptosis in human osteosarcoma line MG63 through PTEN/Akt pathway. Tumour Biol. 2016;37:9333–42.

    Article  CAS  Google Scholar 

  34. Ouyang L, Liu P, Yang S, Ye S, Xu W, Liu X. A three-plasma miRNA signature serves as novel biomarkers for osteosarcoma. Med Oncol. 2013;30:340.

    Article  Google Scholar 

  35. Trang P, Medina PP, Wiggins JF, Ruffino L, Kelnar K, Omotola M, et al. Regression of murine lung tumors by the let-7 microRNA. Oncogene. 2009;29:1580–7.

    Article  Google Scholar 

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Authors and Affiliations

  1. Dental Research Cell (DRC-BRULAC), Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Science (SIMATS), Saveetha University, Chennai, 600077, India

    Durairaj Sekar

  2. Department of Biotechnology, Annai College of Arts and Science, Kumbakonam, Tamil Nadu, 612001, India

    Panagal Mani

  3. Department of Animal Health and Management, Alagappa University, Karaikudi, Tamil Nadu, 630003, India

    M. Biruntha

  4. Department of Microbiology, Faculty of Science, Annamalai University, Chidambaram, Tamil Nadu, 608002, India

    P. Sivagurunathan

  5. Department of Zoology, Arumugam Pillai Seethai Ammal College, Tiruppattur, Tamil Nadu, India

    M. Karthigeyan

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Sekar, D., Mani, P., Biruntha, M. et al. Dissecting the functional role of microRNA 21 in osteosarcoma. Cancer Gene Ther 26, 179–182 (2019). https://doi.org/10.1038/s41417-019-0092-z

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