| Autor: |
Bo Zhan, Xiao Dong, Yulin Yuan, Zheng Gong, Bohan Li |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Frontiers in Oncology, Vol 11 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2234-943X |
| DOI: |
10.3389/fonc.2021.759818 |
| Popis: |
PurposeAccumulating literature has suggested that hZIP1 and HIF-1α play vital roles in the tumor process of clear cell renal cell carcinoma (ccRCC). However, the functional roles of hZIP1 and HIF-1α in ccRCC remain largely unknown.MethodsHIF-1α protein level was evaluated by a western blot in ccRCC tissues and cell lines. ccRCC cell lines were transfected with HIF-1α-siRNA to downregulate the expression level of HIF-1α. Then the proliferative, migratory and invasive abilities of ccRCC cells in vitro were detected by real-time cell analysis (RTCA) assay, wound healing assay and transwell assay, respectively. The role of HIF-1α in vivo was explored by tumor implantation in nude mice. Then the effect on glycolysis‐related proteins was performed by western blot after hZIP1 knockdown (overexpression) or HIF-1α knockdown. The effect on NF‐kB pathway was detected after hZIP1 overexpression.ResultsHIF-1α was markedly downregulated in ccRCC tissues compared with normal areas. But HIF-1α presented almost no expression in HK-2 and ACHN cells. Immunofluorescence indicated HIF-1α and PDK1 expression in both the cytoplasm and nucleus in ccRCC cells. Downregulation of HIF-1α suppressed ccRCC cell proliferation, migration, and invasion and resulted in smaller implanted tumors in nude mice. Furthermore, hZIP1 knockdown elevated HIF-1α protein levels and PDK1 protein levels in ccRCC cells. Interestingly, a sharp downregulated expression of HIF-1α was observed after hZIP1 overexpression in OSRC-2 and 786-O cells, which resulted from a downtrend of NF-kB1 moving into the cell nucleus.ConclusionOur work has vital implications that hZIP1 suppresses ccRCC progression by inhibiting NF-kB/HIF-1α pathway. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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