Solute carrier family 12 member 5 promotes tumor invasion/metastasis of bladder urothelial carcinoma by enhancing NF-κB/MMP-7 signaling pathway.
Solute carrier family 12 member 5 (SLC12A5), an integral membrane KCl cotransporter, which maintains chloride homeostasis in neurons, is aberrantly expressed and involved in the tumorigenesis of certain cancers. However, the clinical significance and biological role of SLC12A5 in human bladder urothelial carcinoma (BUC) remains unclear. In this study, the expression of SLC12A5 was examined in clinical specimens of primary BUC and in BUC cell lines using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry (IHC). The prognostic value of SLC12A5 expression and its correlation with the clinicopathological features of patients with BUC were analyzed statistically. A series of in vitro and in vivo assays were performed to elucidate the effect of SLC12A5 in BUC and its underlying mechanisms. The present results showed that SLC12A5 expression was significantly increased in BUC tissues. SLC12A5 expression significantly correlated with the tumor node metastasis (TNM) stage. Kaplan-Meier survival curves showed that high SLC12A5 expression was associated with poor survival in patients with BUC. Multivariate analysis indicated that SLC12A5 expression was an independent prognostic marker for the survival of patients. Downregulation of SLC12A5 inhibited the migratory and invasive abilities of BUC cells in vitro, and knocking down SLC12A5 diminished BUC metastasis in vivo. Moreover, we identified that SLC12A5 promoted the migration and invasion of BUC by enhancing MMP-7 expression via NF-κB-dependent transcription. Taken together, our findings indicated that SLC12A5 might function as a tumor metastasis promoting factor in the development and progression of BUC by regulating the NF-κB/MMP-7 signaling pathway. Thus, SLC12A5 might be a prognostic marker as well as a therapeutic target for BUC.
Department of Urology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.|Institute of Prostate Disease of Central South University, Changsha 410013, China.
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JY
Liu
Department of Urology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.|Institute of Prostate Disease of Central South University, Changsha 410013, China.
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Dai
Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
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Li
Department of Onology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
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Cao
Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.|State Key Laboratory of Oncology in South China, Guangzhou 510060, China.
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Xie
Department of Radiotherapy, The First Affiliated Hospital of Ahhui Medical University, Anhui 230022, China.
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Tong
Department of Urology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.|Institute of Prostate Disease of Central South University, Changsha 410013, China.
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Long
Department of Pathology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
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Xiao
Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.
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Chen
State Key Laboratory of Oncology in South China, Guangzhou 510060, China.|Department of Urology, Sun Yat-sen University Cancer Center, Guangdong 510060, China.
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Ye
Department of Urology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.|Institute of Prostate Disease of Central South University, Changsha 410013, China.
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B
Liu
Department of Urology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.|Institute of Prostate Disease of Central South University, Changsha 410013, China.
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Tan
Department of Urology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.|Institute of Prostate Disease of Central South University, Changsha 410013, China.
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Tang
Department of Urology, Hunan Cancer Hospital, Changsha 410013, China.
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Xu
Department of Urology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.|Institute of Prostate Disease of Central South University, Changsha 410013, China.
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Gan
Department of Urology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.|Institute of Prostate Disease of Central South University, Changsha 410013, China.
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YH
Zhou
Department of Urology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.|Institute of Prostate Disease of Central South University, Changsha 410013, China.
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Deng
Department of Urology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.|Institute of Prostate Disease of Central South University, Changsha 410013, China.
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He
D014408:Biomarkers, Tumor / Q000235:genetics; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics*; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics; D027981:Symporters / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D000096922:K Cl- Cotransporters
D014408:Biomarkers, Tumor; D020783:Matrix Metalloproteinase 7; D016328:NF-kappa B; D027981:Symporters; C000606816:SLC12A5 protein, human; D000096922:K Cl- Cotransporters; C060932:MMP7 protein, human