3209

HOXA13

Homeobox (HOX) genes, including HOXA13, are involved in human cancer. We found that HOXA13 expression was associated with glioma grade and prognosis. Bioinformatics analysis revealed that most of the HOXA13-associated genes were enriched in cancer-related signaling pathways and mainly involved in the regulation of transcription. We transfected four glioma cell lines with Lenti-si HOXA13. HOXA13 increased cell proliferation and invasion and inhibited apoptosis. HOXA13 decreased beta-catenin, phospho-smad2, and phospho-smad3 in the nucleus and increased phospho-beta-catenin in the cytoplasm. Furthermore, downregulation of HOXA13 in orthotopic tumors decreased tumor growth. We suggest that HOXA13 promotes glioma progression in part via Wnt- and TGF-beta-induced EMT and is a potential diagnostic biomarker for glioblastoma and an independent prognostic factor in high-grade glioma.

OBJECTIVE: To examine the transfection of Homeobox A13 (HOXA13) on epithelial-mesenchymal transition (EMT) and the expression of bone morphogenetic protein-7 (BMP-7) induced by albumin-overload in human kidney tubular epithelial cells (HKCs). METHODS: The cultured HKCs were treated with 20 mg/mL human serum albumin (HSA) for 48 hours. Protein expression of cytokeratin (CK), vimentin and HOXA13 in the HKCs was assessed by Western blot. Protein expression of CK, vimentin, and BMP-7 was also detected in HKCs transfected with lipofectamine contained HOXA13 DNA. RESULTS: HSA induced EMT in HKCs, presented by decreased CK expression (P<0.01) and increased vimentin expression (P<0.01). The up-regulated expression of HOXA13 transfected by lipofectamine inhibited the level of EMT induced by HSA in HKCs (P<0.05). The decreased rate of BMP-7 protein expression induced by HSA was inhibited by over-expressed HOXA13 in HKCs (P<0.05). CONCLUSIONS: Transfection of HOXA13 in HKCs could inhibit the degree of EMT induced by albumin-overload, possibly by increasing BMP-7 expression.

Previous studies have suggested that albumin-induced renal tubular epithelial cell injury contributes to renal interstitial fibrosis. epithelial-mesenchymal transition (EMT) is known to be a key mechanism in the pathogenesis and progression of renal interstitial fibrosis. Homeobox protein HOXA13 (HOXA13) is a nuclear transcriptional factor that has been reported to be involved in renal fibrosis. However, the mechanism underlying the effect of HOXA13 in human serum albumin (HSA)induced EMT in HKC renal tubular epithelial cells remains to be elucidated. Thus, the aim of the present study was to investigate the role of HOXA13 in HSAinduced EMT in HKC cells and the potential mechanism of the glucocorticoid receptor (GR) signaling pathway. The protein and mRNA expression levels of HOXA13, cytokeratin, and vimentin were determined by western blot analysis and reverse transcriptionquantitative polymerase chain reaction in HKC cells, which were coincubated with HSA at different concentrations or for different time periods. The results demonstrated that HOXA13 mRNA and protein expression decreased in a dose and timedependent manner when induced by HSA in HCK cells. The liposomal transfection experiment suggested that overexpression of HOXA13 activated the GR signal, which inhibits HSA-induced EMT. HOXA13 is involved in HSAinduced EMT in HKC cells and upregulation of HOXA13 exerts a beneficial effect in EMT, which may be associated with the GR signaling pathway.

BACKGROUND: Chemoresistance often develops in esophageal squamous cell carcinoma (ESCC), leading to poor prognosis. HOX genes play a crucial role in embryonic development and cell differentiation. Studies have recently linked HOX with chemoresistance, thus we explored whether HOXA13 is involved in ESCC chemoresistance. METHODS: One hundred thirty-one ESCC patients who received neoadjuvant chemotherapy were enrolled. HOXA13 expression was examined by immunohistochemistry. RNA interference was used to knock down the HOXA13 expression in KYSE70 and transfected HOXA13 plasmid to overexpress HOXA13 in KYSE510 cells. We examined half-maximal inhibitory concentration of cisplatin, apoptosis, and epithelial-to-mesenchymal transition (EMT) in ESCC cell lines with different HOXA13 expression levels by cell counting kit-8, flow cytometry, and transwell analysis. RESULTS: The median survival of patients with high HOXA13 expression was significantly shorter than those with low expression (P = 0.027). HOXA13 was associated with worse tumor regression grade (P = 0.009). Low HOXA13 expressed cells decreased the half-maximal inhibitory concentration of cisplatin (P < 0.05), increased cisplatin-induced apoptosis (P < 0.05), and decreased EMT (P < 0.05) compared with high HOXA13 expressed cells. In low HOXA13 expressed cells, cleaved caspase-3 and cleaved PARP expression induced by cisplatin increased, while expression of E-cadherin and Snail protein, markers of EMT, was upregulated and downregulated, respectively. EMT decreased in low HOXA13 expressed cells. CONCLUSION: High HOXA13 expression was associated with inferior tumor regression grade and poor overall survival in ESCC patients treated with neoadjuvant chemotherapy. HOXA13 increased cisplatin-resistance and promoted EMT in ESCC cells.CI - (c) 2018 The Authors. Thoracic cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.