Evaluation of the Expression of Circulating miR-16 and miR-26a in the plasma of Gastric Cancer Patients in Guilan province, North of Iran


Gastric cancer
Real-time quantitative PCR

How to Cite

Babaei Hemmaty, T. ., Ranji, N., & Safari, F. . (2021). Evaluation of the Expression of Circulating miR-16 and miR-26a in the plasma of Gastric Cancer Patients in Guilan province, North of Iran. Iranian Red Crescent Medical Journal, 23(3). https://doi.org/10.32592/ircmj.2021.23.3.214


 Background and Aims: Gastric cancer (GC) is a global health problem and the second deadly type of cancer worldwide with 1000 deaths per year. Poor prognosis in the early stages is one of the burdens in the treatment of GC. MicroRNAs are 18-22 nucleotide non-coding RNAs which play critical roles in the regulation of gene expression. Nowadays, miRNAs are widely known as non-invasive biomarkers for various kinds of cancers. This study aimed to evaluate the expression level of circulating miR-16 and miR-26a in GC patients and investigate the potential prognostic role of these miRNAs.

Material and Methods: Initially, 20 plasma samples were obtained from pre-and post-operative GC patients, and the expression of miR-16 and -26a were compared with that of 20 healthy controls. The miRNAs expression was investigated using Real-Time quantitative PCR. The association between the expression levels of these miRNAs and clinicopathological features was also investigated in this study.

Results: MiR-16 was down-regulated in GC patients; however, miR-26a expression revealed no significant difference between patients and controls in this regard. Furthermore, the expression of two miRNAs showed no association with the grade, TNM stage, and smoking status of the patients. Eventually, decreased expression of miR-16 was not correlated with the expression level of miR-26a.

Conclusion: The downregulation of circulating miR-16 introduces this microRNA as a candidate biomarker for the non-invasive early prognosis of GC.



  1. Hu ML, Xiong SW, Zhu SX, Xue XX, Zhou XD.MicroRNAs in gastric cancer: from bench to bedside. Neoplasma. 2019; 66(2):176-86. doi: 10.4149/neo_2018_180703N439. [PubMed: 30509106].
  2. Zhu C, Huang Q, Zhu H.Melatonin inhibits the proliferation of gastric cancer cells through regulating the mir-16-5p-smad3 pathway. DNA Cell Biol. 2018;37(3): 244-52. doi: 10.1089/dna.2017.4040. [PubMed: 29359963].
  3. Zhang J, Song Y, Zhang C, Zhi X, Fu H, Ma Y, et al. Circulating MiR-16-5p and MiR-19b-3p as Two Novel Potential Biomarkers to Indicate Progression of Gastric Cancer. Theranostics. 2015;5(7):733-45. doi: 10.7150/thno.10305. [PubMed: 25897338].
  4. Digklia A. , Wagner AD. Advanced gastric cancer: Current treatment landscape and future perspectives. World J Gastroenterol. 2016;22(8):2403-14. doi: 10.3748/wjg.v22.i8.2403. [PubMed: 26937129].
  5. Yang SM, Huang C, Li XF, Yu MZ, He Y, Li J. miR-21 confers cisplatin resistance in gastric cancer cells by regulating PTEN. Toxicology. 2013; 306:162-8. doi: 10.1016/j.tox.2013.02.014. [PubMed: 23466500].
  6. Zhao X, Hu GF, Shi YF, Xu W. Research Progress in microRNA-Based Therapy for Gastric Cancer. Onco Targets Ther. 2019;12:11393-411.
  7. 7.      Tehrani FK, Ranji N, Kouhkan F, Hosseinzadeh S.Apoptosis induction and proliferation inhibition by silibinin encapsulated in nanoparticles in MIA PaCa-2 cancer cells and deregulation of some miRNAs. Iran J Basic Med Sci. 2020;23(4):469-82. doi: 10.22038/ijbms.2020.39427.9349. [PubMed: 32489562].
  8. Zadeh MM, Motamed N, Ranji N, Majidi M, Falahi F. Silibinin-induced apoptosis and downregulation of microrna-21 and microrna-155 in mcf-7 human breast cancer cells. J Breast Cancer;2016;19(1):45-52. doi: 10.4048/jbc.2016.19.1.45. [PubMed: 27066095].
  9. Wang H, Peng R, Wang J, Qin Z, Xue L.Circulating microRNAs as potential cancer biomarkers: the advantage and disadvantage. Clin Epigenetics. 2018;10:59. doi: 10.1186/s13148-018-0492-1. [PubMed: 29713393].
  10. Jamali L, Tofigh R, Tutunchi S, Panahi G, Borhani F, Akhavan S. Circulating microRNAs as diagnostic and therapeutic biomarkers in gastric and esophageal cancers. J Cell Physiol. 2018;233(11):8538-50. doi: 10.1002/jcp.26850. [PubMed: 29923196].
  11. Ranji N, Sadeghizadeh M, Shokrgozar MA, Bakhshandeh B, Karimipour M, Amanzadeh A, et al. MiR-17-92 cluster: an apoptosis inducer or proliferation enhancer. Mol Cell Biochem. 2013;380(1-2):229-38. doi: 10.1007/s11010-013-1678-7. [PubMed: 23681423].
  12. Pakizehkar S, Ranji N, Naderi Sohi A, Sadeghizadeh M. Curcumin loaded PEG400-OA nanoparticles: A suitable system to increase apoptosis, decrease migration, and deregulate miR-125b/miR182 in MDA-MB-231 human breast cancer cells. Polymers Advanced Technol. 2020;31(8):1793-804. doi: 10.1002/pat.4906.
  13. O'Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol (Lausanne). 2018;9:402. doi: 10.3389/fendo.2018.00402. [PubMed: 30123182].
  14. Tsai MM, Wang CS, Tsai CY, Huang HW, Chi HC, Lin YH, et al. Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer. Int J Mol Sci. 2016;17(6):945. doi: 10.3390/ijms17060945. [PubMed: 27322246].
  15. Chen B, Guo S, Yu Z, Feng Y, Hui L. Downregulation of microRNA-375, combined with upregulation of its target gene Janus kinase 2, predicts unfavorable prognosis in patients with gastric cancer. Int J Clin Exp Pathol. 2017;10(11):11106-13. [PubMed: 31966459].
  16. Hossainzadeh S, Ranji N, Naderi Sohi A, Najafi F. Silibinin encapsulation in polymersome: A promising anticancer nanoparticle for inducing apoptosis and decreasing the expression level of miR-125b/miR-182 in human breast cancer cells. J Cell Physiol. 2019;234(12):22285-98. doi: 10.1002/jcp.28795. [PubMed: 31073992].
  17. Mohamed JS, Lopez MA, Boriek AM. Mechanical stretch up-regulates microRNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3beta. J Biol Chem. 2010;285(38):29336-47. doi: 10.1074/jbc.M110.101147. [PubMed: 20525681].
  18. Li F, Xu Y, Deng S, Li Z, Zou D, Yi S, et al. MicroRNA-15a/16-1 cluster located at chromosome 13q14 is down-regulated but displays different expression pattern and prognostic significance in multiple myeloma. Oncotarget, 2015;6(35): 38270-82. doi: 10.18632/oncotarget.5681. [PubMed: 26516702].
  19. Braga TV, Evangelista FC, Gomes LC, da Silva Araújo SS, das Graças Carvalho M, de Paula Sabino A.Evaluation of MiR-15a and MiR-16-1 as prognostic biomarkers in chronic lymphocytic leukemia. Biomed Pharmacother. 2017;92:864-9. doi: 10.1016/j.biopha.2017.05.144. [PubMed: 28599250].
  20. Zhan XH, Xu QY, Tian R, Yan H, Zhang M, Wu J, et al. MicroRNA16 regulates glioma cell proliferation, apoptosis and invasion by targeting Wip1-ATM-p53 feedback loop. Oncotarget. 2017;8(33):54788-98. doi: 10.18632/oncotarget.18510. [PubMed: 28903382].
  21. Jiang X, Wang Z. miR-16 targets SALL4 to repress the proliferation and migration of gastric cancer. Oncol Lett. 2018;16(3):3005-12. doi: 10.3892/ol.2018.8997. [PubMed: 30127890].
  22. Deng M, Tang HL, Lu XH, Liu MY, Lu XM, Gu YX, et al. miR-26a suppresses tumor growth and metastasis by targeting FGF9 in gastric cancer. PLoS One; 2013;8(8):e72662. doi: 10.1371/journal.pone.0072662. [PubMed: 24015269].
  23. Si Y, Zhang H, Ning T, Bai M, Wang Y, Yang H, et al. miR-26a/b Inhibit Tumor Growth and Angiogenesis by Targeting the HGF-VEGF Axis in Gastric Carcinoma. Cell Physiol Biochem. 2017;42(4):1670-83. doi: 10.1159/000479412. [PubMed: 28738343].
  24. Wen L, Cheng F, Zhou Y, Yin C. MiR-26a enhances the sensitivity of gastric cancer cells to cisplatin by targeting NRAS and E2F2. Saudi J Gastroenterol. 2015;21(5):313-9. doi: 10.4103/1319-3767.166206. [PubMed: 26458859].
  25. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th Edition of the AJCC Cancer Staging Manual and the Future of TNM. Ann Surg Oncol. 2010;17(6):1471-4. doi: 10.1245/s10434-010-0985-4. [PubMed: 20180029].
  26. 26. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67(1):7-30. doi: 10.3322/caac.21387. [PubMed: 28055103].
  27. Liu L, Chen Q, Lai R, Wu X, Wu X, Liu F, et al. Elevated expression of mature miR-21 and miR-155 in cancerous gastric tissues from Chinese patients with gastric cancer. J Biomed Res, 2010. 24(3):187-97. doi: 10.1016/S1674-8301(10)60028-0. [PubMed: 23554630].
  28. Link A, Kupcinskas J. MicroRNAs as non-invasive diagnostic biomarkers for gastric cancer: Current insights and future perspectives. World J Gastroenterol. 2018;24(30):3313-29. doi: 10.3748/wjg.v24.i30.3313. [PubMed: 30122873].
  29. Ranji N, Sadeghizadeh M, Karimipoor M, Shokrgozar MA, Sistani RN, Paylakhi SH.MicroRNAs Signature in IL-2-Induced CD4+ T Cells and Their Potential Targets. Biochem Genet. 2015;53(7-8): p. 169-83. doi: 10.1007/s10528-015-9677-x. [PubMed: 26048624].
  30. Wang T, Hou J, Li Z, Zheng Z, Wei J, Song D, et al.miR-15a-3p and miR-16-1-3p Negatively Regulate Twist1 to Repress Gastric Cancer Cell Invasion and Metastasis. Int J Biol Sci. 2017;13(1):122-34. doi: 10.7150/ijbs.14770. [PubMed: 28123352].
  31. Li HH, Wang JD, Wang W, Wang HF, Lv JQ.. Effect of miR-26a-5p on gastric cancer cell proliferation, migration and invasion by targeting COL10A1. Eur Rev Med Pharmacol Sci.2020;24(3):1186-94. doi: 10.26355/eurrev_202002_20170. [PubMed: 32096148].
  32. Reid G, Kirschner MB, van Zandwijk N. Circulating microRNAs: Association with disease and potential use as biomarkers. Crit Rev Oncol Hematol.2011;80(2):193-208. doi: 10.1016/j.critrevonc.2010.11.004. [PubMed: 21145252].
  33. Ma Q, Wang X, Li Z, Li B, Ma F, Peng L, et al. microRNA-16 represses colorectal cancer cell growth in vitro by regulating the p53/survivin signaling pathway. Oncol Rep. 2013;29(4):1652-8. doi: 10.3892/or.2013.2262. [PubMed: 23380758].
  34. Zhou Q, Han LR, Zhou YX, Li Y. MiR-195 Suppresses Cervical Cancer Migration and Invasion Through Targeting Smad3. Int J Gynecol Cancer. 2016;26(5):817-24. doi: 10.1097/IGC.0000000000000686. [PubMed: 27206216].
  35. Zhou HH, Chen L, Liang HF, Li GZ, Zhang BX, Chen XP. Smad3 Sensitizes Hepatocelluar Carcinoma Cells to Cisplatin by Repressing Phosphorylation of AKT. Int J Mol Sci. 2016;17(4):610. doi: 10.3390/ijms17040610. [PubMed: 27110775].
  36. Tatetsu H, Kong NR, Chong G, Amabile G, Tenen DG, Chai L. SALL4, the missing link between stem cells, development and cancer. Gene. 2016;584(2):111-9. doi: 10.1016/j.gene.2016.02.019. [PubMed: 26892498].
  37. Lin K, Farahani M, Yang Y, Johnson GG, Oates M, Atherton M, et al. Loss of MIR15A and MIR16-1 at 13q14 is associated with increased TP53 mRNA, de-repression of BCL2 and adverse outcome in chronic lymphocytic leukaemia. Br J Haematol. 2014;167(3):346-55. doi: 10.1111/bjh.13043. [PubMed: 25040181].