Welcome to visit Zhongnan Medical Journal Press Series journal website!

Effects of KCNN4 on the biological functions of prostate cancer cells

Published on Feb. 25, 2025Total Views: 24 timesTotal Downloads: 11 timesDownloadMobile

Author: WANG Danqi 1, 2 XI Shu 1, 2 CUI Jinlong 1, 2 WANG Shichun 1 ZHANG Jia 1, 2 SHI Minghui 1, 2 YUAN Shuai 1 ZENG Xiantao 1, 2

Affiliation: 1. Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China 2. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China

Keywords: KCNN4 Prostate cancer Ion channels Proliferation Migration

DOI: 10.12173/j.issn.1004-5511.202412060

Reference: Wang DQ, Xi S, Cui JL, Wang SC, Zhang J, Shi MH, Yuan S, Zeng XT. Effects of KCNN4 on the biological functions of prostate cancer cells[J]. Yixue Xinzhi Zazhi, 2025, 35(2): 168-174. DOI: 10.12173/j.issn.1004-5511.202412060.[Article in Chinese]

  • Abstract
  • Full-text
  • References
Abstract

Objective To investigate the biological function of the intermediate-conductance calcium-activated potassium channel (KCNN4) and the inhibitory effect of its small molecule inhibitor, Senicapoc, in prostate cancer.

Methods  Small interfering RNA (siRNA)-mediated KCNN4 knockdown was performed in DU145 and C4-2 cell lines. Cell counting kit- 8 (CCK-8) assays, Transwell assays, and wound-healing assays were conducted to evaluate the changes in cell proliferation and migration. The cell lines WPMY-1, 22RV-1, C4-2, and DU145 were treated with Senicapoc. The effects of Senicapoc on cell proliferation and migration were assessed using CCK-8 assays, colony formation assays, and wound-healing assays.

Results Downregulation of KCNN4 significantly reduced cell viability and cell migration (P<0.05). Senicapoc treatment significantly decreased cell viability, colony numbers, and migration rates (P<0.05).

Conclusion  KCNN4 promotes the proliferation and migration of prostate cancer cells. Targeting KCNN4 may represent a novel therapeutic strategy for prostate cancer.

Full-text
Please download the PDF version to read the full text: download
References

1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263. DOI: 10.3322/caac.21834.

2. Zi H, Liu MY, Luo LS, et al. Global burden of benign prostatic hyperplasia, urinary tract infections, urolithiasis, bladder cancer, kidney cancer, and prostate cancer from 1990 to 2021[J]. Mil Med Res, 2024, 11(1): 64. DOI: 10.1186/s40779-024-00569-w.

3. Tilki D, van den Bergh RCN, Briers E, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on prostate cancer. Part II-2024 update: treatment of relapsing and metastatic prostate cancer[J]. Eur Urol, 2024, 86(2): 164-182. DOI: 10.1016/j.eururo. 2024.04.010.

4. Siegel DA, O'Neil ME, Richards TB, et al. Prostate cancer incidence and survival, by stage and race/ethnicity-United States, 2001-2017[J]. MMWR Morb Mortal Wkly Rep, 2020, 69(41): 1473-1480. DOI: 10.15585/mmwr.mm6941a1.

5. Prevarskaya N, Skryma R, Shuba Y. Ion channels in cancer: are cancer hallmarks oncochannelopathies?[J]. Physiol Rev, 2018, 98(2): 559-621. DOI: 10.1152/physrev.00044.2016.

6. Xia C, Liu C, Ren S, et al. Potassium channels, tumorigenesis and targeted drugs[J]. Biomed Pharmacother, 2023, 162: 114673. DOI: 10.1016/j.biopha.2023.114673.

7. Thi Hong Van N, Hyun Nam J. Intermediate conductance calcium-activated potassium channel (KCa3.1) in cancer: emerging roles and therapeutic potentials[J]. Biochem Pharmacol, 2024, 230(Pt 1): 116573. DOI: 10.1016/j.bcp.2024.116573.

8. Ohya S, Kimura K, Niwa S, et al. Malignancy grade-dependent expression of K+-channel subtypes in human prostate cancer[J]. J Pharmacol Sci, 2009, 109(1): 148-151. DOI: 10.1254/jphs. 08208SC.

9. Prevarskaya N, Skryma R, Shuba Y. Ion channels and the hallmarks of cancer[J]. Trends Mol Med, 2010, 16(3): 107-121. DOI: 10.1016/j.molmed.2010.01.005.

10. Bortner CD, Cidlowski JA. Ion channels and apoptosis in cancer[J]. Philos Trans R Soc Lond B Biol Sci, 2014, 369(1638): 20130104. DOI: 10.1098/rstb.2013.0104.

11. Lehen'kyi V, Shapovalov G, Skryma R, et al. Ion channnels and transporters in cancer. 5. Ion channels in control of cancer and cell apoptosis[J]. Am J Physiol Cell Physiol, 2011, 301(6): C1281-1289. DOI: 10.1152/ajpcell.00249.2011.

12. Stejerean-Todoran I, Bogeski I. Malignant currents: sodium leak channel NALCN propels prostate cancer aggressiveness[J]. EMBO J, 2023, 42(19): e114986. DOI: 10.15252/embj.2023114986.

13. Arcangeli A, Becchetti A. Novel perspectives in cancer therapy: targeting ion channels[J]. Drug Resist Updat, 2015, 21-22: 11-19. DOI: 10.1016/j.drup.2015.06.002.

14. Chávez-López MG, Zúñiga-García V, Hernández-Gallegos E, et  al. The combination astemizole-gefitinib as a potential therapy for human lung cancer[J]. Onco Targets Ther, 2017, 10: 5795-5803. DOI: 10.2147/OTT.S144506.

15. Li Z, Huang L, Wei L, et al. KCNH3 predicts poor prognosis and promotes progression in ovarian cancer[J]. Onco Targets Ther, 2020, 13: 10323-10333. DOI: 10.2147/OTT.S268055.

16. Morales P, Garneau L, Klein H, et al. Contribution of the KCa3.1 channel-calmodulin interactions to the regulation of the KCa3.1 gating process[J]. J Gen Physiol, 2013, 142(1): 37-60. DOI: 10.1085/jgp.201210933.

17. Brown BM, Pressley B, Wulff H. KCa3.1 channel modulators as potential therapeutic compounds for glioblastoma[J]. Curr Neuropharmacol, 2018, 16(5): 618-626. DOI: 10.2174/1570159X15666170630164226.

18. Van NTH, Kim WK, Nam JH. Challenges in the therapeutic targeting of KCa channels: from basic physiology to clinical applications[J]. Int J Mol Sci, 2024, 25(5): 2965. DOI: 10.3390/ijms25052965.

19. Ohya S, Matsui M, Kajikuri J, et al. Downregulation of IL-8 and IL-10 by the activation of Ca2+-activated K+ channel KCa3.1 in THP-1-derived M2 Macrophages[J]. Int J Mol Sci, 2022, 23(15): 8603. DOI: 10.3390/ijms23158603.

20. Chen S, Su X, Mo Z. KCNN4 is a potential biomarker for predicting cancer prognosis and an essential molecule that remodels various components in the tumor microenvironment: a pan-cancer study[J]. Front Mol Biosci, 2022, 9: 812815. DOI: 10.3389/fmolb.2022.812815.

21. Mo X, Zhang CF, Xu P, et al. KCNN4-mediated Ca2+/MET/AKT axis is promising for targeted therapy of pancreatic ductal adenocarcinoma[J]. Acta Pharmacol Sin, 2022, 43(3): 735-746. DOI: 10.1038/s41401-021-00688-3.

22. Xu P, Mo X, Xia R, et al. KCNN4 promotes the progression of lung adenocarcinoma by activating the AKT and ERK signaling pathways[J]. Cancer Biomark, 2021, 31(2): 187-201. DOI: 10.3233/CBM-201045.

23. Li QT, Feng YM, Ke ZH, et al. KCNN4 promotes invasion and metastasis through the MAPK/ERK pathway in hepatocellular carcinoma[J]. J Investig Med, 2020, 68(1): 68-74. DOI: 10.1136/jim-2019-001073.

24. Ibrahim S, Chaigne J, Dakik H, et al. SK4 oncochannels regulate calcium entry and promote cell migration in KRAS-mutated colorectal cancer[J]. Cell Calcium, 2021, 96: 102384. DOI: 10.1016/j.ceca.2021.102384.