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HNF‑4α 下调通过调节肾细胞癌中的 E‑钙黏蛋白促进肿瘤迁移和侵袭。

HNF‑4α downregulation promotes tumor migration and invasion by regulating E‑cadherin in renal cell carcinoma.

机构信息

Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China.

Department of Anesthesiology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China.

出版信息

Oncol Rep. 2019 Sep;42(3):1066-1074. doi: 10.3892/or.2019.7214. Epub 2019 Jun 27.

Abstract

Renal cell carcinoma (RCC) is the most common malignant disease of the kidneys in adults. Patients with metastatic RCC have an unusually poor prognosis and exhibit resistance to all current therapies. Therefore, it is necessary to explore novel molecules involved in the progression of RCC and to identify effective therapeutic targets. Hepatocyte nuclear factor‑4α (HNF‑4α) serves an important role in hepatocyte differentiation and is involved in the progression of liver cancer; however, the functional role of HNF‑4α has not been well established in RCC. The present study reported that HNF‑4α expression was markedly downregulated in RCC tissue samples compared with in normal controls by immunohistochemistry and RNA‑sequencing analysis. Statistical analysis demonstrated that HNF‑4α downregulation was significantly associated with tumor stage, recurrence, metastasis and poor prognosis in patients with RCC. Furthermore, wound‑healing and Transwell assays revealed that downregulation of HNF‑4α promoted cell migration and invasion by transcriptionally regulating E‑cadherin in RCC. Finally, a positive correlation was revealed between HNF‑4α expression and E‑cadherin expression, and patients with low E‑cadherin expression also had a poor prognosis. These findings may provide novel insights into the biological effects of HNF‑4α and lay the foundation for the discovery of molecular therapeutic targets in RCC.

摘要

肾细胞癌(RCC)是成年人肾脏最常见的恶性疾病。转移性 RCC 患者的预后异常差,并对所有现有疗法均产生耐药性。因此,有必要探索参与 RCC 进展的新型分子,并确定有效的治疗靶点。肝细胞核因子-4α(HNF-4α)在肝细胞分化中起重要作用,并参与肝癌的进展;然而,HNF-4α 在 RCC 中的功能作用尚未得到充分证实。本研究通过免疫组织化学和 RNA 测序分析报道,与正常对照相比,HNF-4α 在 RCC 组织样本中的表达明显下调。统计学分析表明,HNF-4α 的下调与 RCC 患者的肿瘤分期、复发、转移和预后不良显著相关。此外,划痕和 Transwell 实验表明,通过转录调控 E-钙黏蛋白,下调 HNF-4α 促进了 RCC 细胞的迁移和侵袭。最后,发现 HNF-4α 表达与 E-钙黏蛋白表达之间呈正相关,E-钙黏蛋白低表达的患者预后也较差。这些发现可能为 HNF-4α 的生物学效应提供新的见解,并为发现 RCC 的分子治疗靶点奠定基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ba/6667891/1198cf12bb64/or-42-03-1066-g00.jpg

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