Original Article

Mechanism of miRNA-26a on the Proliferation of Pancreatic Tumor Cells by Regulating the Expression of Cycline2


Background: qRT-PCR was used to measure the expression of miRNA-26a in pancreatic epithelial cells (HPDE) and human pancreatic cancer cell lines PANC-1 and MIA PaCa-2.

Methods: PANC-1 and MIA PaCa-2 cell lines were infected with lentiviruses to construct PANC-miR-26a and MIA-miR-26a, and RT-PCR was used to detect the infection efficiency. The cell proliferation ability of PANC-miR-26a and MIA-miR-26a were examined by CCK-8 assay, and apoptosis was detected by flow cytometry. Western blotting was used to detect the expressions of CyclinE2 protein and mitochondria-associated apoptotic proteins. 

Results: miR-26a was expressed in human normal pancreatic epithelial cells (HPDE), and not detected in PANC-1 and MIA PaCa-2; miR-26a was highly expressed in the cell lines PANC-miR-26a and MIA-miR-26a infected by the virus particles. The absorbance values of PANC-miR-26a and MIA-miR-26a were lower than those of NC1 and PANC-1 in control group. The apoptosis rates of PANC-miR-26a and MIA-miR-26a were substantially higher than those of the control group. The overexpression of miR-26a inhibited the expression of the target protein CyclinE2 in PANC-miR-26a and MIA-miR-26a. The expression of the anti-apoptotic protein Bcl-2 was decreased in PANC-miR-26a and MIA-miR-26a, while the expression of the pro-apoptotic protein Bax was increased. Compared with HPDE, miR-26a was down-regulated in PANC-1 and MIA PaCa-2. After overexpression of miR-26a, the proliferation of PANC-1 and MIA PaCa-2 cell lines was weakened.

Conclusion: Molecular mechanism is the negative regulation of CyclinE2 by miR-26a as well as the expressions of downstream mitochondrial apoptosis proteins Bcl-2 and Bax.


1. McGuigan A, Kelly P, Turkington RC, et al (2018). Pancreatic cancer: A review of clinical diagnosis, epidemiology, treat-ment, and outcomes. World J Gastroenterol, 24: 4846–4861.
2. Zhang L, Sanagapalli S, Stoita A (2018). Challenges in the diagnosis of pancreatic cancer. World J Gastroenterol, 24: 2047–2060.
3. Rawla P, Sunkara T, Gaduputi V (2019). Ep-idemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World J Oncol, 10: 10–27.
4. Ren B, Cui M, Yang G, et al (2018). Tumor microenvironment participates in metas-tasis of pancreatic cancer. Mol Cancer, 17: 108.
5. Słotwiński R, Lech G, Słotwińska SM (2018). MicroRNAs in pancreatic cancer diagnosis and therapy. Cent Eur J Immunol, 43: 314–324.
6. Lee RC, Feinbaum RL, Ambros V (1993). The C. elegansheterochronic gene lin-4 encodes small RNAs with Antisense Complementarity to lin-14. Cell, 75: 843-854.
7. Bhome R, Del Vecchio F, Lee GH, et al (2018). Exosomal microRNAs (exomiRs): Small molecules with a big role in cancer. Cancer Lett, 420: 228–235.
8. Zhang Q, Wang Q, Zhang Y, et al (2018). Comprehensive Analysis of Mi-croRNA⁻Messenger RNA from White Yak Testis Reveals the Differentially Ex-pressed Molecules Involved in improve-mentand Reproduction. Int J Mol Sci, 19: 3083.
9. Bartel DP (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116: 281-297.
10. Ma L, Liang Z, Zhou H, Qu L (2018). Ap-plications of RNA Indexes for Precision Oncology in Breast Cancer. Genomics Pro-teomics Bioinformatics, 16: 108–119.
11. Paladini L, Fabris L, Bottai G, Raschioni C, Calin GA, Santarpia L (2016). Targeting microRNAs as key modulators of tumor immune response. J Exp Clin Cancer Res, 35: 103.
12. Liu J, Gao J, Du Y, et al (2012). Combina-tion of plasma micro RNAs with serum CA19-9 for early detection of pancreatic cancer. Int J Cancer, 131: 683-691.
13. Li J, Sun CK (2018). In vitro analysis of mi-croRNA-26a in chronic lymphocytic leu-kemia cells. Int J Mol Med, 42: 3364–3370.
14. Liu X, Song B, Li S, Wang N, Yang H (2017). Identification and functional anal-ysis of the risk microRNAs associated with cerebral low-grade glioma progno-sis. Mol Med Rep, 16: 1173–1179.
15. Cheng Q, Tang L, Wang Y (2018). Regula-tory role of miRNA-26a in neonatal sep-sis. Exp Ther Med, 16: 4836–4842.
16. Chen S, Qi X, Chen H, et al (2016). Expres-sion of miRNA-26a in platelets is associ-ated with clopidogrel resistance following coronary stenting. Exp Ther Med, 12: 518–524.
17. Lin Y, Chen F, Shen L, et al (2018). Bi-omarker microRNAs for prostate cancer metastasis: screened with a network vul-nerability analysis model. J Transl Med, 16: 134.
18. Yang J, Sheng YY, Wei JW, et al (2018). Mi-croRNA-219-5p Promotes Tumor Growth and Metastasis of Hepatocellular Carcinoma by Regulating Cadherin 1. Bi-omed Res Int, 2018: 4793971.
19. Chen L, Zheng J, Zhang Y (2011). Tumor-specific expression of micro RNA-26a growth via cyclin-dependent and -independent pathways. Mother, 19: 1521-1528.
20. Tang SC, Chen YC (2014). Novel therapeu-tic targets for pancreatic cancer. World J Gastroenterol, 20: 10825–10844.
21. Deng J, He M, Chen L, Chen C, Zheng J, Cai Z (2013). The loss of miR-26a-mediated post-transcriptional regulation of cyclin E2 in pancreatic cancer cell pro-liferation and decreased patient survival. PLoS One, 8: e76450.
22. Jackson A, Linsley PS (2010). The therapeu-tic potential of microRNA modulation. Discov Med, 9: 311-318.
23. Krishnan P, Damaraju S (2018). The Chal-lenges and Opportunities in the Clinical Application of Noncoding RNAs: The Road Map for miRNAs and piRNAs in Cancer Diagnostics and Prognostics. Int J Genomics, 2018: 5848046.
24. Wood DJ, Endicott JA (2018). Structural in-sights into the functional diversity of the CDK-cyclin family. Open Biol, 8: 180112.
25. Menzel P, McCorkindale AL, Stefanov SR, Zinzen RP, Meyer IM (2019). Transcrip-tional dynamics of microRNAs and their targets during Drosophila neurogenesis. RNA Biol, 16: 69–81.
26. Nakazawa M, Matsubara H, Matsushita Y, et al (2016). The human Bcl-2 family mem-ber Bcl-Rambo localizes to mitochondria and induces apoptosis and morphologi-cal aberrations in Drosophila. PLoS ONE, 11: e0157823.
27. Edison N, Curtz Y, Paland N, et al (2017). Degradation of Bcl-2 by XIAP and ARTS promotes apoptosis. Cell Rep, 21: 442-454.
28. Dai G, Zheng D, Guo W, Yang J, Cheng AY (2018). Cinobufagin Induces Apop-tosis in Osteosarcoma Cells Via the Mi-tochondria-Mediated Apoptotic Pathway. Cell Physiol Biochem, 46: 1134-1147.
29. Liang G, Kan S, Zhu Y, Feng S, Feng W, Gao S (2018). Engineered exosome-mediated delivery of functionally active miR-26a and its enhanced suppression effect in HepG2 cells. Int J Nanomedicine, 13: 585–599.
30. Gong Y, Wu W, Zou X, Liu F, Wei T, Zhu J (2018). MiR-26a inhibits thyroid cancer cell proliferation by targeting ARPP19. Am J Cancer Res, 8: 1030–1039.
31. Wang H, Hu Z, Chen L (2018). Enhanced plasma miR-26a-5p promotes the pro-gression of bladder cancer via targeting PTEN. Oncol Lett, 16: 4223–4228.
32. Fukumoto I, Hanazawa T, Kinoshita T, et al (2015). MicroRNA expression signature of oral squamous cell carcinoma: func-tional role of microRNA-26a/b in the modulation of novel cancer pathways. Br J Cancer, 112: 891–900.
33. Zhao CX, Zhu W, Ba ZQ, et al (2018). The regulatory network of nasopharyngeal carcinoma metastasis with a focus on EBV, lncRNAs, and miRNAs. Am J Can-cer Res, 8: 2185–2209.
34. Cabello P, Pineda B, Tormo E, Lluch A, Eroles P (2016). The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer. Int J Mol Sci, 17: 1298.
35. Kota J, Chivukula RR, O'Donnell KA, et al (2009). Therapeutic micro RNA delivery suppresses tumorigenesis in a murine liv-er cancer model. Cell, 137: 1005-1017.
36. Lu J, He ML, Wang L, et al (2011). MiR-26a Inhibits Cell Growth and Tumorigenesis of Nasopharyngeal Carcinoma through Repression of EZH2. Cancer Res, 71: 225-233.
37. Sander S, Bullinger L, Klapproth K, et al (2008). MYC stimulates EZH2 its nega-tive regulator miR-26a. Blood, 112: 4202-4212.
IssueVol 49 No 6 (2020) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v49i6.3366
Cycline2; miRNA-26a; Pancreatic cancer

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How to Cite
HOU X, XU J, HU P. Mechanism of miRNA-26a on the Proliferation of Pancreatic Tumor Cells by Regulating the Expression of Cycline2. Iran J Public Health. 2020;49(6):1138-1147.