Work

Silencing of voltage-gated potassium channel KV9.3 inhibits proliferation in human colon and lung carcinoma cells

Year: 2015

Type: article

Abstract: // Jeong-Ha Lee 1 , Jun-Won Park 2 , Jun Kyu Byun 3 , Hark Kyun Kim 2 , Pan Dong Ryu 3 , So Yeong Lee 3 and Dae-Yong Kim 1 1 Laboratory of Veterinary Pathology, Seoul National University, Seoul, Korea 2 Biomolecular Function Research Branch, National Cancer Center, Goyang, Gyeonggi, Korea 3 Veterinary Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea Correspondence to: Dae-Yong Kim, email: // So Yeong Lee, email: // Keywords : cancer, colon, K v 9.3, lung, proliferation Received : December 09, 2014 Accepted : February 03, 2015 Published : April 10, 2015 Abstract Voltage-gated potassium (K v ) channels are known to be involved in cancer development and cancer cell proliferation. K V 9.3, an electronically silent subunit, forms heterotetramers with K V 2.1 in excitable cells and modulates its electrophysiological properties. However, the role of K V 9.3 alone in non-excitable cancer cells has not been studied. Here, we evaluated the effect of silencing K V 9.3 on cancer cell proliferation in HCT15 colon carcinoma cells and A549 lung adenocarcinoma cells. We confirmed the expression of K V 9.3 mRNA in HCT15 and A549 cells and showed that silencing K V 9.3 using small interfering RNA caused G0/G1 cell cycle arrest and alterations in cell cycle regulatory proteins in both HCT15 and A549 cells without affecting apoptosis. Also, stable knockdown of K V 9.3 expression using short-hairpin RNA inhibited tumor growth in SCID mouse xenograft model. Using a bioinformatics approach, we identified Sp1 binding sites in the promoter region of the gene encoding K V 9.3. We further found that Sp1 bound to this region and showed that the Sp1 inhibitor, mithramycin A, induced a concentration-dependent decrease in K V 9.3 expression. Taken together, these data suggest that knockdown of K V 9.3 inhibits proliferation in colon carcinoma and lung adenocarcinoma cell lines and may be regulated by Sp1.

Source: Oncotarget

DOI: 10.18632/oncotarget.3517