Login Register Cart 0
Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Downregulation of miRNA-14669 Reverses Vincristine Resistance in Colorectal Cancer Cells through PI3K/AKT Signaling Pathway

Author(s): Weihua Dong, Fang Wang, Qingyu Liu, Tianyun Wang*, Yun Yang, Peixia Guo, Xiang Li and Bingdi Wei

Volume 17, Issue 2, 2022

Published on: 06 August, 2021

Page: [178 - 186] Pages: 9

DOI: 10.2174/1574892816666210806154225

Price: $65

Abstract

Background: Vincristine (VCR) is a chemotherapeutic drug commonly used in the treatment of Colorectal Cancer (CRC). However, VCR drug resistance may result in reduced efficacy and even failure of chemotherapy in CRC treatment. MiRNA has been demonstrated to be associated with the sensitivity of tumor cells to chemotherapy.

Objectives: This study aimed to identify a novel miRNA-14669 that can reverse vincristine resistance and sensitize drug-resistant colorectal cancer cells.

Methods: High-throughput sequencing was performed to screen miRNAs that are associated with VCR drug resistance, and qRT-PCR was used for further validation. The miRNA mimic and inhibitor were designed and transfected into HCT-8,HCT-116 and HCT-8/VCR cells. Wound healing test examined the effect of the miRNA on the migration of colorectal cancer cells. Flow cytometry was used to evaluate cell apoptosis of HCT-8 cells. Survivin, Bcl-2, GST3, MDR1 and MRP1 expressions were detected by Western blot.

Results: The expression of miRNA-14669 in HCT-8/VCR cells was 1.925 times higher than that of the HCT-8 cells. After transfecting with mimic miRNA, HCT-8 and HCT-116 cells showed an increased survival rate. The survival rate of HCT-8/VCR cells decreased by transfection of inhibitor. The inhibitor also sensitized HCT-8 and HCT-116 cells to VCR or 5-Fluorouracil (5-FU). The migratory ability of HCT-8 and HCT-116 cells increased by miRNA mimic while reduced by miRNA inhibitor. Overexpression of miRNA-14669 reduced apoptosis, while downregulation of miRNA- 14669 increased cell apoptosis in HCT-8 cells. The mechanism of the miRNA involved in drug resistance may be attributed to apoptosis of tumor cells, detoxification of GST3 and drug efflux induced by MDR1 and MRP1. PI3K / AKT is the signaling pathway related to drug resistance.

Conclusion: We identified a novel miRNA-14669 that may be associated with the chemotherapeutic resistance in CRC cells.

Keywords: miRNA, identify, drug resistance, colorectal cancer, reverse, regulation.

« Previous Next »
[1]
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65(2): 87-108.
[http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]
[2]
Kathawala RJ, Gupta P, Ashby CR Jr, Chen ZS. The modulation of ABC transporter-mediated multidrug resistance in cancer: A review of the past decade. Drug Resist Updat 2015; 18: 1-17.
[http://dx.doi.org/10.1016/j.drup.2014.11.002] [PMID: 25554624]
[3]
Hede K. Studies define role of microRNA in cancer. J Nati Cancer Inst 2005; 97(15): 1114-5.
[4]
Bartel DP. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004; 116(2): 281-97.
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438]
[5]
Shukla GC, Singh J, Barik S. MicroRNAs: Processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol 2011; 3(3): 83-92.
[PMID: 22468167]
[6]
Xishan Z, Ziying L, Jing D, Gang L. MicroRNA-320a acts as a tumor suppressor by targeting BCR/ABL oncogene in chronic myeloid leukemia. Sci Rep 2015; 5: 12460.
[http://dx.doi.org/10.1038/srep12460] [PMID: 26228085]
[7]
Zhang ZL, Bai ZH, Wang XB, Bai L, Miao F, Pei HH. miR-186 and 326 predict the prognosis of pancreatic ductal adenocarcinoma and affect the proliferation and migration of cancer cells. PLoS One 2015; 10(3): e0118814.
[http://dx.doi.org/10.1371/journal.pone.0118814] [PMID: 25742499]
[8]
Tejero R, Navarro A, Campayo M, et al. miR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma. PLoS One 2014; 9(7): e101899.
[http://dx.doi.org/10.1371/journal.pone.0101899] [PMID: 25003366]
[9]
Yang Z, Wang R, Zhang T, Dong X. MicroRNA-126 regulates migration and invasion of gastric cancer by targeting CADM1. Int J Clin Exp Pathol 2015; 8(8): 8869-80.
[PMID: 26464628]
[10]
Fordham JB, Naqvi AR, Nares S. Regulation of miR-24, miR-30b, and miR-142-3p during macrophage and dendritic cell differentiation potentiates innate immunity. J Leukoc Biol 2015; 98(2): 195-207.
[http://dx.doi.org/10.1189/jlb.1A1014-519RR] [PMID: 25990241]
[11]
Dong WH, Li Q, Zhang XY, Guo Q, Li H, Wang TY. Deep sequencing identifies deregulation of microRNAs involved with vincristine drug-resistance of colon cancer cells. Int J Clin Exp Pathol 2015; 8(9): 11524-30.
[PMID: 26617885]
[12]
Zou J, Yin F, Wang Q, Zhang W, Li L. Analysis of microarray-identified genes and microRNAs associated with drug resistance in ovarian cancer. Int J Clin Exp Pathol 2015; 8(6): 6847-58.
[PMID: 26261572]
[13]
Riquelme I, Letelier P, Riffo-Campos AL, Brebi P, Roa JC. Emerging role of miRNAs in the drug resistance of gastric cancer. Int J Mol Sci 2016; 17(3): 424.
[http://dx.doi.org/10.3390/ijms17030424] [PMID: 27011182]
[14]
To KK. MicroRNA: A prognostic biomarker and a possible druggable target for circumventing multidrug resistance in cancer chemotherapy. J Biomed Sci 2013; 20(1): 99.
[http://dx.doi.org/10.1186/1423-0127-20-99] [PMID: 24358977]
[15]
Baranwal S, Alahari SK. miRNA control of tumor cell invasion and metastasis. Int J Cancer 2010; 126(6): 1283-90.
[http://dx.doi.org/10.1002/ijc.25014] [PMID: 19877123]
[16]
Wu Q, Yang Z, Xia L, et al. Methylation of miR-129-5p CpG island modulates multi-drug resistance in gastric cancer by targeting ABC transporters. Oncotarget 2014; 5(22): 11552-63.
[http://dx.doi.org/10.18632/oncotarget.2594] [PMID: 25344911]
[17]
Ward A, Shukla K, Balwierz A, et al. MicroRNA-519a is a novel oncomir conferring tamoxifen resistance by targeting a network of tumour-suppressor genes in ER+ breast cancer. J Pathol 2014; 233(4): 368-79.
[http://dx.doi.org/10.1002/path.4363] [PMID: 24752803]
[18]
Liu RL, Dong Y, Deng YZ, Wang WJ, Li WD. Tumor suppressor miR-145 reverses drug resistance by directly targeting DNA damage-related gene RAD18 in colorectal cancer. Tumour Biol 2015; 36(7): 5011-9.
[http://dx.doi.org/10.1007/s13277-015-3152-5] [PMID: 25913620]
[19]
Liang Z, Wu H, Xia J, et al. Involvement of miR-326 in chemotherapy resistance of breast cancer through modulating expression of multidrug resistance-associated protein 1. Biochem Pharmacol 2010; 79(6): 817-24.
[http://dx.doi.org/10.1016/j.bcp.2009.10.017] [PMID: 19883630]
[20]
O’Brien K, Lowry MC, Corcoran C, et al. miR-134 in extracellular vesicles reduces triple-negative breast cancer aggression and increases drug sensitivity. Oncotarget 2015; 6(32): 32774-89.
[http://dx.doi.org/10.18632/oncotarget.5192] [PMID: 26416415]
[21]
Fang L, Li H, Wang L, et al. MicroRNA-17-5p promotes chemotherapeutic drug resistance and tumour metastasis of colorectal cancer by repressing PTEN expression. Oncotarget 2014; 5(10): 2974-87.
[http://dx.doi.org/10.18632/oncotarget.1614] [PMID: 24912422]
[22]
Zhang Y, Geng L, Talmon G, Wang J. MicroRNA-520g confers drug resistance by regulating p21 expression in colorectal cancer. J Biol Chem 2015; 290(10): 6215-25.
[http://dx.doi.org/10.1074/jbc.M114.620252] [PMID: 25616665]
[23]
Amankwatia EB, Chakravarty P, Carey FA, et al. MicroRNA-224 is associated with colorectal cancer progression and response to 5-fluorouracil-based chemotherapy by KRAS-dependent and -independent mechanisms. Br J Cancer 2015; 112(9): 1480-90.
[http://dx.doi.org/10.1038/bjc.2015.125] [PMID: 25919696]
[24]
Liu Z, Zhu H, Qu S, et al. Pyramidatine (Z88) sensitizes vincristine-resistant human oral cancer (KB/VCR) cells to chemotherapeutic agents by inhibition of p-glycoprotein. Anticancer Agents Med Chem 2018; 18(2): 286-94.
[http://dx.doi.org/10.2174/1871520617666170803155025] [PMID: 28782465]
[25]
Nagayama S, Chen ZS, Kitazono M, et al. Increased sensitivity to vincristine of MDR cells by the leukotriene D4 receptor antagonist, ONO-1078. Cancer Lett 1998; 130(1-2): 175-82.
[http://dx.doi.org/10.1016/S0304-3835(98)00132-3] [PMID: 9751271]
[26]
Akbari Moqadam F, Lange-Turenhout EA, Ariës IM, Pieters R, den Boer ML. MiR-125b, miR-100 and miR-99a co-regulate vincristine resistance in childhood acute lymphoblastic leukemia. Leuk Res 2013; 37(10): 1315-21.
[http://dx.doi.org/10.1016/j.leukres.2013.06.027] [PMID: 23915977]
[27]
Due H, Schönherz AA, Ryø L, et al. MicroRNA-155 controls vincristine sensitivity and predicts superior clinical outcome in diffuse large B-cell lymphoma. Blood Adv 2019; 3(7): 1185-96.
[28]
Han J, Liu Z, Wang N, Pan W. MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X-linked inhibitor of apoptosis protein. Oncol Rep 2016; 36(1): 542-50.
[http://dx.doi.org/10.3892/or.2016.4810] [PMID: 27221209]
[29]
Ye J, Wang Z, Zhao J, et al. MicroRNA-141 inhibits tumor growth and minimizes therapy resistance in colorectal cancer. Mol Med Rep 2017; 15(3): 1037-42.
[http://dx.doi.org/10.3892/mmr.2017.6135] [PMID: 28112364]
[30]
Jiang W. Application of miR-4527 in diagnosis or treatment of tumor drug resistance. ZL 202011384422 .5, China, 2020.
[31]
Wu Y, Guo L, Liu J, Liu R, Liu M, Chen J. The reversing and molecular mechanisms of miR-503 on the drug resistance to Cisplatin in A549/DDP cells. Chin J Lung Cancer 2014; 17(1): 1-7.
[32]
Eslami F, Mahdavi M, Babaei E, et al. Down-regulation of Survivin and Bcl-2 concomitant with the activation of caspase-3 as a mechanism of apoptotic death in KG1a and K562 cells upon exposure to a derivative from ciprofloxacin family. Toxicol Appl Pharmacol 2020; 409(409): 115331.
[http://dx.doi.org/10.1016/j.taap.2020.115331] [PMID: 33171188]
[33]
El-Ashmawy NE, Khedr EG, El-Bahrawy HA, Helmy NN. Modulatory effect of silymarin on apoptosis in testosterone - induced benign prostatic hyperplasia in rats. Pathol Oncol Res 2020; 26(3): 1947-56.
[http://dx.doi.org/10.1007/s12253-019-00764-4] [PMID: 31902118]
[34]
Wu X, Dai L, Zhang Z, Zheng J, Zhao J. Overexpression of microRNA-203 can downregulate survivin and function as a potential therapeutic target in papillary thyroid cancer. Oncol Lett 2020; 19(1): 61-8.
[PMID: 31897115]
[35]
Negoro R, Kawai K, Ichikawa M, Deguchi S, Takayama K, Mizuguchi H. Establishment of MDR1-knockout human induced pluripotent stem cell line. Drug Metab Pharmacokinet 2020; 35(3): 288-96.
[http://dx.doi.org/10.1016/j.dmpk.2020.01.009] [PMID: 32303458]
[36]
Li NN, Guo Y, Jiang CJ, et al. Allyl isothiocyanate upregulates MRP1 expression through Notch1 signaling in human bronchial epithelial cells. Can J Physiol Pharmacol 2020; 98(5): 324-31.
[http://dx.doi.org/10.1139/cjpp-2019-0448] [PMID: 31747319]
[37]
Larson RS, Sklar LA, Edwards BS, et al. Selective efflux inhibitors and related pharmaceutical compositions and methods of treatment. US9056111B1, USA, 2015.
[38]
Gangjee A. Tricyclic compounds having antimitotic and/or antitumor activity and methods of us thereof . US9056869B2, USA, 2015.
[39]
Sefidgari-Abrasi S, Roshangar L, Karimi P, Morshedi M, Rahimiyan-Heravan M, Saghafi-Asl M. From the gut to the heart: L. plantarum and inulin administration as a novel approach to control cardiac apoptosis via 5-HT2B and TrkB receptors in diabetes. Clin Nutr 2021; 40(1): 190-201.
[http://dx.doi.org/10.1016/j.clnu.2020.05.004] [PMID: 32446786]
[40]
Zhang L, Chen H, Song Y, et al. MiR-325 promotes oxaliplatin-induced cytotoxicity against colorectal cancer through the HSPA12B/PI3K/AKT/Bcl-2 pathway. Dig Dis Sci 2020; 66(8): 2651-60.
[41]
Xiong Y, Lu H, Xu H. Galangin Reverses Hepatic Fibrosis by Inducing HSCs Apoptosis via the PI3K/Akt, Bax/Bcl-2, and Wnt/β- Catenin Pathway in LX-2 Cells. Biol Pharm Bull 2020; 43(11): 1634-42.
[http://dx.doi.org/10.1248/bpb.b20-00258] [PMID: 32893252]
[42]
Zhang L, Li Y, Wang Q, et al. The PI3K subunits, P110α and P110β are potential targets for overcoming P-gp and BCRP-mediated MDR in cancer. Mol Cancer 2020; 19(1): 10.
[http://dx.doi.org/10.1186/s12943-019-1112-1] [PMID: 31952518]
[43]
Dong WH, Wang TY, Zhang JH, Gao JH, Yan ZY, Ni TY. Primers, kit, method and applications for detecting miRNA expression related to vincristine resistance in colorectal cancer. ZL201710129192X, China, 2017.

Rights & Permissions Print Cite
Article Metrics
39
2
© 2024 Bentham Science Publishers | Privacy Policy