RESUMO
It has been well documented that changes in ion fluxes across cellular membranes is fundamental in maintaining cellular homeostasis. Dysregulation and/or malfunction of ion channels are critical events in the pathogenesis of diverse diseases, including cancers. In this study, we focused on the study of K+ channels in hepatocellular carcinoma (HCC). By data mining TCGA cohort, the expression of 27 K+ channels was investigated and KCNJ11 was identified as a key dysregulated K+ channels in HCC. KCNJ11 was differentially expressed in HCC and predicted a poor prognosis in HCC patients. Inhibition of NFκB signaling suppressed KCNJ11 expression in HCC cells. Knockdown of KCNJ11 expression inhibited cell proliferation, promoted cell apoptosis, and reduced cell invasive capacity. Mechanistically, we found that KCNJ11 promotes tumor progression through interaction with LDHA and enhancing its enzymatic activity. Pharmacological inhibition of LDHA largely compromised the oncogenic function of KCNJ11 in cell proliferation, cell apoptosis, and cell invasion. Collectively, our data, as a proof of principle, demonstrate that KCNJ11 acts as an oncogene in HCC though forming a complex with LDHA and suggest that targeting KCNJ11 can be developed as a candidate tool to dampen HCC.
Assuntos
Carcinoma Hepatocelular/patologia , L-Lactato Desidrogenase/metabolismo , Neoplasias Hepáticas/patologia , Fígado/patologia , NF-kappa B/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Mapas de Interação de Proteínas , Apoptose , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Isoenzimas/metabolismo , Lactato Desidrogenase 5 , Fígado/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , PrognósticoRESUMO
By applying density functional theory calculations to iron chalcogenides, we find that magnetic order in Fe1+yTe and magnetic instability at (π, π) in KyFe2Se2 are controlled by interstitial and interlayer cations, respectively. While in Fe1+yTe, magnetic phase transitions occur among collinear, exotic bicollinear and plaquette-ordered antiferronmagnetic states when the height of interstitial irons measured from iron plane or the concentration of interstitial irons is varied, the magnetic instability at (π, π) which is believed to be responsible for the Cooper pairing in iron pnictides is significantly enhanced when y is much smaller than 1 in KyFe2Se2. Our results indicate that, similar to iron pnictides, itinerant electrons play important roles in iron chalcogenides, even though the fluctuating local moments become larger.