Document Type : Research articles
Authors
1 Department of Oncology, Second People Hospital of Dezhou, Dezhou, Shandong Province, China
2 Department of Endoscopic, Second People Hospital of Dezhou, Dezhou, Shandong Province, China
3 Department of Radiotherapy, Second People Hospital of Dezhou, Dezhou, Shandong Province, China
Abstract
Objectives: This study aimed to investigate the potential function of miR-214 in the apoptosis induction by targeting p53 in human colorectal cancer cells (CRC) in combination with doxorubicin (DOX).
Methods: miR-214 mimics were transfected to HT-29 CRC cells. Following that, the transfected cells were treated with DOX. Cell viability, apoptosis, and migration were evaluated by MTT, flow cytometry, and scratch-wound motility assays, respectively. Furthermore, the expression level of miR-214 and p53 was evaluated by qRT-PCR.
Results: miR-214 transfection significantly inhibited the cell proliferation rate (P<0.05), induced apoptosis (P<0.05), and harnessed migration (P<0.05) in the HT-29 cells after 48 h. Furthermore, more effectiveness was observed in combination with DOX. Additionally, miR-214 transfection led to a reduction in p53 expression offering that it might be a potential target for miR-214.
Conclusion: In conclusion, miR-214 sensitizes HT-29 cells to doxorubicin by targeting p53 indicating the significant role of this miRNA in colorectal cancer chemotherapy.
Keywords
- Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics. CA Cancer J Clin. 2020;70(3):145-64. doi: 10.3322/caac.21601. [PubMed: 32133645].
- Kamarudin MN, Sarker MM, Zhou JR, Parhar I. Metformin in colorectal cancer: molecular mechanism, preclinical and clinical aspects. J Exp Clin Cancer Res. 2019;38(1):491. doi: 10.1186/s13046-019-1495-2. [PubMed: 31831021].
- Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14(2):89-103. doi: 10.5114/pg.2018.81072. [PubMed: 31616522].
- Kim HG, Kim HS, Yang SY, Han YD, Cho MS, Hur H, et al. Early recurrence after neoadjuvant chemoradiation therapy for locally advanced rectal cancer: Characteristics and risk factors. Asian J Surg. 2020;S1015-9584(20):30226-8. doi: 10.1016/j.asjsur.2020.07.014. [PubMed: 32718796].
- Van der Jeught K, Xu HC, Li YJ, Lu XB, Ji G. Drug resistance and new therapies in colorectal cancer. World J Gastroenterol. 2018;24(34):3834-48. doi: 10.3748/wjg.v24.i34.3834. [PubMed: 30228778].
- 6 Tang XJ, Wang W, Hann SS. Interactions among lncRNAs, miRNAs and mRNA in colorectal cancer. Biochimie. 2019;163:58-72. doi: 10.1016/j.biochi.2019.05.010. [PubMed: 31082429].
- Hu W, Tan C, He Y, Zhang G, Xu Y, Tang J. Functional miRNAs in breast cancer drug resistance. OncoTargets Ther. 2018;11:1529-41. doi: 10.2147/OTT.S152462. [PubMed: 29593419].
- Luu HN, Lin HY, Sørensen KD, Ogunwobi OO, Kumar N, Chornokur G, et al. miRNAs associated with prostate cancer risk and progression. BMC Uroly. 2017;17(1):18. doi: 10.1186/s12894-017-0206-6. [PubMed: 28320379].
- Cortez MA, Anfossi S, Ramapriyan R, Menon H, Atalar SC, Aliru M, et al. Role of miRNAs in immune responses and immunotherapy in cancer. Genes Chromosomes Cancer. 2019;58(4):244-53. doi: 10.1002/gcc.22725. [PubMed: 30578699].
- Liu B, Tian Y, Li F, Zhao Z, Jiang X, Zhai C, et al. Tumor-suppressing roles of miR-214 and miR-218 in breast cancer. Oncol Rep. 2016;35(6):3178-84. doi: 10.3892/or.2016.4749. [PubMed: 27109339].
- Liu B, Liu Q, Pan S, Huang Y, Qi Y, Li S, et al. The HOTAIR/miR-214/ST6GAL1 crosstalk modulates colorectal cancer procession through mediating sialylated c-Met via JAK2/STAT3 cascade. J Exp Clin Cancer Res. 2019;38(1):455. doi: 10.1186/s13046-019-1468-5. [PubMed: 31694696].
- Yang H, Kong W, He L, Zhao JJ, O'Donnell JD, Wang J, et al. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 2008;68(2):425-33. doi: 10.1158/0008-5472.CAN-07-2488. [PubMed: 18199536].
- Long LM, He BF, Huang GQ, Guo YH, Liu YS, Huo JR. MicroRNA-214 functions as a tumor suppressor in human colon cancer via the suppression of ADP-ribosylation factor-like protein 2. Oncol Lett. 2015;9(2):645-50. doi: 10.3892/ol.2014.2746. [PubMed: 25621032].
- Wang F, Liu M, Li X, Tang H. MiR-214 reduces cell survival and enhances cisplatin-induced cytotoxicity via down-regulation of Bcl2l2 in cervical cancer cells. FEBS lett. 2013;587(5):488-95. doi: 10.1016/j.febslet.2013.01.016. [PubMed: 23337879].
- Wang X, Zhang H, Bai M, Ning T, Ge S, Deng T, et al. Exosomes serve as nanoparticles to deliver anti-miR-214 to reverse chemoresistance to cisplatin in gastric cancer. Mol Ther. 2018;26(3):774-83. doi: 10.1016/j.ymthe.2018.01.001. [PubMed: 29456019].
- Zhang J, Liu J, Xu X, Li L. Curcumin suppresses cisplatin resistance development partly via modulating extracellular vesicle-mediated transfer of MEG3 and miR-214 in ovarian cancer. Cancer Chemother Pharmacol. 2017;79(3):479-87. doi: 10.1007/s00280-017-3238-4. [PubMed: 28175963].
- Xu M, Chen X, Lin K, Zeng K, Liu X, Xu X, et al. lncRNA SNHG6 regulates EZH2 expression by sponging miR-26a/b and miR-214 in colorectal cancer. J Hematol Oncol. 2019;12(1):3. doi: 10.1186/s13045-018-0690-5. [PubMed: 30626446].
- Chen DL, Wang ZQ, Zeng ZL, Wu WJ, Zhang DS, Luo Hy, et al. Identification of microRNA‐214 as a negative regulator of colorectal cancer liver metastasis by way of regulation of fibroblast growth factor receptor 1 expression. Hepatology. 2014;60(2):598-609. doi: 10.1002/hep.27118. [PubMed: 24616020].
- Sun R, Liu Z, Han L, Yang Y, Wu F, Jiang Q, et al. miR‐22 and miR‐214 targeting BCL9L inhibit proliferation, metastasis, and epithelial‐mesenchymal transition by down‐regulating Wnt signaling in colon cancer. FASEB J. 2019;33(4):5411-24. doi: 10.1096/fj.201801798RR. [PubMed: 30698996].
- Nie H, Nie D, Men L. Role of miR-214 in modulating proliferation and invasion of human colon cancer SW620 cells. Oncol Lett. 2018;16(6):7175-9. doi: 10.3892/ol.2018.9521. [PubMed: 30546454].
- Liu J, Bi J, Li Z, Li Z, Liu X, Kong C. miR‑214 reduces cisplatin resistance by targeting netrin‑1 in bladder cancer cells. Int J Mol Med. 2018;41(3):1765-73. doi: 10.3892/ijmm.2018.3374. [PubMed: 29328435].
- Yang Y, Bao Y, Yang G-K, Wan J, Du L-J, Ma Z-HJC, et al. MiR-214 sensitizes human colon cancer cells to 5-FU by targeting Hsp27. Cell Mol Biol Lett. 2019;24:22. doi: 10.1186/s11658-019-0143-3. [PubMed: 30915129].
- Zhang J, Su B, Gong C, Xi Q, Chao T. miR-214 promotes apoptosis and sensitizes breast cancer cells to doxorubicin by targeting the RFWD2-p53 cascade. Biochem Biophys Res Commun. 2016;478(1):337-42. doi: 10.1016/j.bbrc.2016.07.054. [PubMed: 27422604].
- Wu K, Ma J, Zhan Y, Liu K, Ye Z, Chen J, et al. Down-regulation of microRNA-214 contributed to the enhanced mitochondrial transcription factor a and inhibited proliferation of colorectal Cancer cells. Cell Physiol Biochem. 2018;49(2):545-54. doi: 10.1159/000492992. [PubMed: 30157478].
- Xu CX, Xu M, Tan L, Yang H, Permuth-Wey J, Kruk PA, et al. MicroRNA MiR-214 regulates ovarian cancer cell stemness by targeting p53/Nanog. J Biol Chem. 2016;291(43):22851. doi: 10.1074/jbc.A112.374611. [PubMed: 27825089].
- Wang F, Lv P, Liu X, Zhu M, Qiu X. microRNA-214 enhances the invasion ability of breast cancer cells by targeting p53. Int J Mol Med. 2015;35(5):1395-402. doi: 10.3892/ijmm.2015.2123. [PubMed: 25738546].
- Zhang J, Su B, Gong C, Xi Q, Chao T. miR-214 promotes apoptosis and sensitizes breast cancer cells to doxorubicin by targeting the RFWD2-p53 cascade. Biochem Biophys Res Commun. 2016;478(1):337-42. doi: 10.1016/j.bbrc.2016.07.054. [PubMed: 27422604]
', './data/ircmj/coversheet/cover_en.jpg'))