Low expression of KCNN3 may affect drug resistance in ovarian cancer

Abstract

Drug resistance is a principal contributor to the poor prognosis of ovarian cancer (OC). Therefore, identifying factors that affect drug resistance in OC is critical. In the present study, 51 OC specimens from lab collections were immunohistochemically tested, public data for 489 samples from The Cancer Genome Atlas cohort and 1,656 samples from the Kaplan-Meier Plotter were downloaded, and data were retrieved from Oncomine. It was identified that the mRNA and protein expression of the potassium calcium-activated channel subfamily N member 3 (KCNN3) was markedly lower in OC tissues compared with normal tissues, and in drug-resistant OC tissues compared with sensitive OC tissues. Low KCNN3 expression consistently predicted shorter disease-free and overall survival (OS). Specifically, low KCNN3 expression predicted shorter OS in 395 patients with low expression levels of mucin-16. There was additional evidence that KCNN3 expression is mediated by microRNA-892b. Furthermore, text mining and analyses of protein and gene interactions indicated that KCNN3 affects drug resistance. To the best of the authors' knowledge, this is the first report to associate KCNN3 with poor prognosis and drug resistance in OC. The present findings indicated that KCNN3 is a potential prognostic marker and therapeutic target for OC.

KCNN4 is a diagnostic and prognostic biomarker that promotes papillary thyroid cancer progression

“…The Potassium Calcium-Activated Channel Subfamily N (KCNN) family includes four proteins (KCNN1-KCNN4) that constitute a heterotetrameric voltage-independent potassium channel. The KCNNs are involved in various cancers: low KCNN3 expression promotes drug resistance and may predict a poor prognosis in ovarian cancer [ 27 ], high KCNN4 expression is associated with poor survival in pancreatic cancer patients [ 28 ], and KCNN2 is overexpressed in proximal tumors compared to distal tumors in colorectal cancer [ 29 ]. However, the involvement of the KCNN family in TC is still unknown.…”

Ion Channels: New Actors Playing in Chemotherapeutic Resistance

“…Both overexpression and reduction of K + channels expression are involved in chemosensitivity. For example, using big data analysis, Liu et al demonstrated an association between the reduction of KCNN3 expression (a gene encoding for the SK3 K + channel) and drug resistance of ovarian cancer [102]. Similar associations were reported on the classically used cisplatin [103].…”

Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

“…The KCNN3 gene encoding the calcium-activated K + channel KCa2.3 was predicted to be one of 1298 genes contributing to drug resistance in OC [203]. Using immunohistochemistry and big data analyses, Liu and collaborators found a significantly lower expression of KCNN3 in drug-resistant OC tissues, confirming an involvement of KCa2.3 channels in drug resistance (Figure 2) [114,122]. It was further hypothesized that KCa2.3 and TRPC1 may act in concert in drug resistance through inhibition of drug-induced cell death [204].…”

“…Recent studies revealed an involvement of KCa2.3 (KCNN3 gene) and KCa3.1 (KCNN4 gene) in OC pathogenesis [122,123]. KCNN3 mRNA expression was significantly lower in OC tissues compared with normal controls, suggesting its negative contribution in OC progression [122].…”