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TUSC3 通过抑制 AKT 信号通路抑制宫颈鳞状细胞癌细胞增殖和侵袭。

TUSC3 inhibits cell proliferation and invasion in cervical squamous cell carcinoma via suppression of the AKT signalling pathway.

机构信息

Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Provincial Clinical Research Center for Thalassemia, the Key Laboratory of Tropical Translational Medicine of Ministry of Education, Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, P.R. China.

Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangdong, China.

出版信息

J Cell Mol Med. 2022 Mar;26(5):1629-1642. doi: 10.1111/jcmm.17204. Epub 2022 Feb 9.

Abstract

The decreased expression of tumour suppressor candidate 3 (TUSC3) is associated with proliferation in several types of cancer, leading to an unfavourable prognosis. The present study aimed to assess the cellular and molecular function of TUSC3 in patients with cervical squamous cell carcinoma (CSCC). Levels of mRNA expressions of TUSC3 were analysed in CSCC tissues and six cell lines using qRT-PCR. Immunohistochemistry(IHC) was used to evaluate the protein expression level of TUSC3 in four paired specimens, 220 paraffin-embedded CSCC specimens and 60 cases of normal cervical tissues(NCTs), respectively. Short hairpin RNA interference was employed for TUSC3 knockdown. Cell proliferation, migration and invasion were evaluated using growth curve, MTT assay, wound healing, transwell assay and xenograft tumour model, respectively. The results demonstrated that TUSC3 mRNA and protein expression levels were downregulated in CSCC samples. Multivariate and univariate analyses indicated that TUSC3 was an independent prognostic factor for patients with CSCC. Decreased TUSC3 expression levels were significantly associated with proliferation and an aggressive phenotype of cervical cancer cells both in vitro and in vivo. Moreover, the knockdown of TUSC3 promoted migration and invasion of cancer cells, while the increased expression of TUSC3 exhibited the opposite effects. The downregulation of TUSC3 facilitated proliferation and invasion of CSCC cells through the activation of the AKT signalling pathway. Our data demonstrated that the downregulation of TUSC3 promoted CSCC cell metastasis via the AKT signalling pathway. Therefore, TUSC3 may serve as a novel prognostic marker and potential target for CSCC.

摘要

抑癌候选基因 3(TUSC3)的表达下调与多种类型癌症的增殖有关,导致预后不良。本研究旨在评估 TUSC3 在宫颈鳞状细胞癌(CSCC)患者中的细胞和分子功能。使用 qRT-PCR 分析了 CSCC 组织和六种细胞系中 TUSC3 的 mRNA 表达水平。免疫组织化学(IHC)分别评估了四对标本、220 例石蜡包埋 CSCC 标本和 60 例正常宫颈组织(NCT)中 TUSC3 的蛋白表达水平。采用短发夹 RNA 干扰进行 TUSC3 敲低。通过生长曲线、MTT 测定、划痕愈合、Transwell 测定和异种移植肿瘤模型分别评估细胞增殖、迁移和侵袭。结果表明,TUSC3 在 CSCC 样本中的 mRNA 和蛋白表达水平下调。多变量和单变量分析表明,TUSC3 是 CSCC 患者的独立预后因素。TUSC3 表达水平降低与体外和体内宫颈癌的增殖和侵袭表型显著相关。此外,TUSC3 的敲低促进了癌细胞的迁移和侵袭,而 TUSC3 的表达增加则表现出相反的效果。TUSC3 的下调通过激活 AKT 信号通路促进 CSCC 细胞的增殖和侵袭。我们的数据表明,TUSC3 的下调通过 AKT 信号通路促进 CSCC 细胞的转移。因此,TUSC3 可能作为一种新的 CSCC 预后标志物和潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eed/8899155/9865c2364676/JCMM-26-1629-g001.jpg

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