Hemodialysis Room, The 7th Hospital of Wuhan, Wuhan, 430071 Hubei, China.
Department of Stomatology, First People's Hospital of Zaoyang City, Zaoyang, 441100 Hubei, China.
Anal Cell Pathol (Amst). 2022 May 19;2022:4213401. doi: 10.1155/2022/4213401. eCollection 2022.
Clear cell renal cell carcinoma (ccRCC) is the major histopathological subtype of renal cancer, and ferroptosis is implicated in the pathogenesis of ccRCC. The present study was aimed at investigating the role and underlying mechanisms of microRNA-4735-3p (miR-4735-3p) in ccRCC.
Human ccRCC cell lines were transfected with the miR-4735-3p mimic or inhibitor to manipulate the expression of miR-4735-3p. Cell proliferation, colony formation, cell migration, cell invasion, cell death, oxidative stress, lipid peroxidation, and iron metabolism were determined. To validate the necessity of solute carrier family 40 member 1 (SLC40A1), human ccRCC cell lines were overexpressed with SLC40A1 using adenoviral vectors.
miR-4735-3p expression was reduced in human ccRCC tissues and cell lines but elevated upon ferroptotic stimulation. The miR-4735-3p mimic increased, while the miR-4735-3p inhibitor decreased oxidative stress, lipid peroxidation, iron overload, and ferroptosis of human ccRCC cell lines. Mechanistic studies identified SLC40A1 as a direct target of miR-4735-3p, and SLC40A1 overexpression significantly attenuated iron overload and ferroptosis in the miR-4735-3p mimic-treated human ccRCC cell lines.
miR-4735-3p facilitates ferroptosis and tumor suppression in ccRCC by targeting SLC40A1.
透明细胞肾细胞癌（ccRCC）是肾癌的主要组织病理学亚型，铁死亡与 ccRCC 的发病机制有关。本研究旨在探讨微小 RNA-4735-3p（miR-4735-3p）在 ccRCC 中的作用及其潜在机制。
用 miR-4735-3p 模拟物或抑制剂转染人 ccRCC 细胞系，以操纵 miR-4735-3p 的表达。测定细胞增殖、集落形成、细胞迁移、细胞侵袭、细胞死亡、氧化应激、脂质过氧化和铁代谢。为了验证溶质载体家族 40 成员 1（SLC40A1）的必要性，用人腺病毒载体过表达 SLC40A1。
miR-4735-3p 在人 ccRCC 组织和细胞系中表达降低，但在铁死亡刺激时升高。miR-4735-3p 模拟物增加，而 miR-4735-3p 抑制剂降低人 ccRCC 细胞系的氧化应激、脂质过氧化、铁过载和铁死亡。机制研究表明 SLC40A1 是 miR-4735-3p 的直接靶标，SLC40A1 过表达显著减轻了 miR-4735-3p 模拟物处理的人 ccRCC 细胞系中的铁过载和铁死亡。
miR-4735-3p 通过靶向 SLC40A1 促进 ccRCC 中的铁死亡和肿瘤抑制。
