Original Article

The Effect of SLC2A3 Expression on Cisplatin Resistance of Colorectal Cancer Cells

Abstract

Background: To study the molecular mechanism of cisplatin chemotherapy resistance in colorectal cancer cells and to explore the effect of miRNA in regulating the expression of glucose transporter 3 (SLC2A3) and the proliferation and migration of colon cancer cells.

Methods: All samples were obtained from the People’s Hospital of Wuhai, Wuhai, China between June 2019 and June 2020. Real-time quantitative PCR (qRT-PCR) was carried out to check the expression of miR-103a in these cell lines. Western blotting and Luciferase reporter gene detection confirmed the regulation of the miR-103a/SLC2A3 axis. Western blotting detected the activation of SLC2A3, caspased-9 and -3.

Results: The expression of SLC2A3 protein in colon cancer cell lines was significantly higher than that of normal colon cancer cells, while the expression of SLC2A3 miRNA showed no significant difference (P<0.05). Then, through clone formation analysis, SLC2A3 was closely related to the proliferation of human colon cancer cells. Functional recovery experiments showed that increasing the expression of miR-103a could reverse the abnormal proliferation caused by overexpression of SLC2A3.

Conclusion: Overall, miR-103a can inhibit the proliferation of human colon cancer cells by targeting SLC2A3, and this result will provide a potential target for the treatment of colon cancer.

1. Auclin E, Zaanan A, Vernerey D, et al (2017). Subgroups and prognostication in stage III colon cancer: future perspectives for adjuvant therapy. Ann Oncol, 28(5): 958-68.
2. Karim S, Brennan K, Nanji S, et al (2017). Association Between Prognosis and Tu-mor Laterality in Early-Stage Colon Can-cer. JAMA Oncol, 3(10): 1386-92.
3. Salem ME, Yin J, Goldberg RM, et al (2020). Evaluation of the change of outcomes over a 10-year period in patients with stage III colon cancer: pooled analysis of 6501 patients treated with fluorouracil, leucovorin, and oxaliplatin in the AC-CENT database. Ann Oncol, 31(4): 480-6.
4. Shi C, Ding K, Li KZ, et al (2020). Com-prehensive analysis of location-specific hub genes related to the pathogenesis of colon cancer. Med Oncol, 237(9): 77.
5. Tarazona N, Gimeno-Valiente F, Gam-bardella V, et al (2019). Targeted next-generation sequencing of circulating-tumor DNA for tracking minimal residu-al disease in localized colon cancer. Ann Oncol, 30(11): 1804-12.
6. Waissbluth S, Daniel SJ (2013). Cisplatin-induced ototoxicity: transporters playing a role in cisplatin toxicity. Hear Res, 299: 37-45.
7. Li Q, Zhang J, Zhou J, et al (2018). lncRNAs are novel biomarkers for dif-ferentiating between cisplatin-resistant and cisplatin-sensitive ovarian cancer. On-col Lett, 15(6): 8363-70.
8. Melnikov SV, Soll D, Steitz TA, et al (2016). Insights into RNA binding by the anti-cancer drug cisplatin from the crystal structure of cisplatin-modified ribosome. Nucleic Acids Res, 44(10): 4978-87.
9. Schlormann W, Naumann S, Renner C, et al (2015). Influence of miRNA-106b and miRNA-135a on butyrate-regulated ex-pression of p21 and Cyclin D2 in human colon adenoma cells. Genes Nutr, 10(6): 50.
10. Xiao B, Viennois E, Chen Q, et al (2018). Si-lencing of Intestinal Glycoprotein CD98 by Orally Targeted Nanoparticles En-hances Chemosensitization of Colon Cancer. ACS Nano, 12(6): 5253-65.
11. Xu H, Wang X, Wu J, et al (2020). Long Non-coding RNA LINC01094 Promotes the Development of Clear Cell Renal Cell Carcinoma by Upregulating SLC2A3 via MicroRNA-184. Front Genet, 11: 562967.
12. Akao Y, Kumazaki M, Shinohara H, et al (2018). Impairment of K-Ras signaling networks and increased efficacy of epi-dermal growth factor receptor inhibitors by a novel synthetic miR-143. Cancer Sci, 109(5): 1455-67.
13. Zhang Y, Wang Z, Chen M, et al (2012). MicroRNA-143 targets MACC1 to inhib-it cell invasion and migration in colorectal cancer. Mol Cancer, 11: 23.
14. Zampetaki A, Attia R, Mayr U, et al (2014). Role of miR-195 in aortic aneurysmal dis-ease. Circ Res, 115(10): 857-66.
15. Zhang Q, Zhang C, Ma JX, et al (2019). Circular RNA PIP5K1A promotes colon cancer development through inhibiting miR-1273a. World J Gastroenterol, 25(35): 5300-9.
16. Yao X, He Z, Qin C, et al (2020). SLC2A3 promotes macrophage infiltration by gly-colysis reprogramming in gastric cancer. Cancer Cell Int, 20: 503.
17. Chen D, Wang H, Chen J, et al (2018). Mi-croRNA-129-5p Regulates Glycolysis and Cell Proliferation by Targeting the Glu-cose Transporter SLC2A3 in Gastric Cancer Cells. Front Pharmacol, 9: 502.
18. Lee J, You JH, Shin D, Roh JL (2020). Inhi-bition of Glutaredoxin 5 predisposes Cisplatin-resistant Head and Neck Can-cer Cells to Ferroptosis. Theranostics, 10(17): 7775-7786.
19. Makovec T (2019). Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiol Oncol, 53(2): 148-158.
Files
IssueVol 50 No 12 (2021) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v50i12.7941
Keywords
Colon cancer MiRNA Cisplatin resistance
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Li Y, Lei H, Zhang M, Wu G, Guo C, Yang Z, Zhang J, Wang Y, Zhu J, Du Y. The Effect of SLC2A3 Expression on Cisplatin Resistance of Colorectal Cancer Cells. Iran J Public Health. 2021;50(12):2576-2583.