Cao Junyu, Jiang Peng, Jiang Songliang, Zhao Yuhan, Jiang Xin, Zhou Chuancheng, Li Jing, Yang Kunxian
Department of Breast and Thyroid Surgery, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Endokrynol Pol. 2025 May 7. doi: 10.5603/ep.104958.
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal malignancies. The MiR-22 host gene (MIR22HG) has been identified as a novel long non-coding RNA (lncRNA) in a few types of cancer. Nevertheless, little is known about the potential role of MIR22HG in ATC. In this study, we aimed to investigate the biological functions and underlying molecular mechanisms of MIR22HG in ATC.
The expression of MIR22HG in tissues and cells of ATC were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viabilities and invasive abilities were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, wound healing assay, and Matrigel invasion assay. The mechanism of MIR22HG interacting with microRNA-141-3p (miR-141-3p) was measured by RNA immunoprecipitation (RIP) assay, RNA pull-down assay, and dual-luciferase reporter assay.
MIR22HG was downregulated in ATC tissues and cells. More importantly, decreased expression of MIR22HG was found to be correlated with poor prognosis of ATC patients. Functional analysis showed that overexpression of MIR22HG attenuated the proliferation and metastasis of ATC both in vitro and in vivo. Mechanistically, MIR22HG positively modulated phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression via sponging miR-141-3p, thus inhibiting downstream protein kinase B (AKT) signaling cascade.
MIR22HG serves as a tumor suppressor in ATC and impedes the progression of ATC through regulation of miR-141-3p/PTEN/AKT axis. Our findings illustrate the critical role of the MIR22HG/miR-141-3p/PTEN/AKT axis in the progression of ATC, which offers new insights for the therapeutic strategies of ATC.
间变性甲状腺癌（ATC）是最具侵袭性和致死性的恶性肿瘤之一。MiR-22宿主基因（MIR22HG）已被确定为几种癌症中的一种新型长链非编码RNA（lncRNA）。然而，关于MIR22HG在ATC中的潜在作用知之甚少。在本研究中，我们旨在探讨MIR22HG在ATC中的生物学功能及潜在分子机制。
采用定量实时聚合酶链反应（qRT-PCR）检测ATC组织和细胞中MIR22HG的表达。通过3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐（MTT）法、伤口愈合试验和基质胶侵袭试验评估细胞活力和侵袭能力。通过RNA免疫沉淀（RIP）试验、RNA下拉试验和双荧光素酶报告试验检测MIR22HG与微小RNA-141-3p（miR-141-3p）相互作用的机制。
MIR22HG在ATC组织和细胞中表达下调。更重要的是，发现MIR22HG表达降低与ATC患者的不良预后相关。功能分析表明，MIR22HG的过表达在体外和体内均减弱了ATC的增殖和转移。机制上，MIR22HG通过海绵吸附miR-141-3p正向调节第10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）的表达，从而抑制下游蛋白激酶B（AKT）信号级联反应。
MIR22HG在ATC中作为肿瘤抑制因子，通过调节miR-141-3p/PTEN/AKT轴阻碍ATC的进展。我们的研究结果阐明了MIR22HG/miR-141-3p/PTEN/AKT轴在ATC进展中的关键作用，为ATC的治疗策略提供了新的见解。
