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富含脯氨酸的蛋白 1A 促进肺腺癌的进展并预示着不良的临床结局。

Small proline-rich protein 1A promotes lung adenocarcinoma progression and indicates unfavorable clinical outcomes.

机构信息

Department of Respiratory Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200336, China.

出版信息

Biochem Cell Biol. 2022 Jun 1;100(3):199-212. doi: 10.1139/bcb-2021-0348. Epub 2022 Mar 9.

Abstract

Small proline-rich protein 1A (SPRR1A) plays a critical role in regulating squamous cell differentiation. SPRR1A overexpression was reported to be closely related to the progression of some tumors, such as gastric cancer and colon cancer. However, the function of SPRR1A in lung adenocarcinoma (LUAD) has not been elucidated. Here, we first examined the expression pattern of SPRR1A in LUAD tissues, which indicated that the SPRR1A expression level was significantly elevated in LUAD tissues compared with normal lung tissues. High expression of SPRR1A was closely related to larger tumor size. LUAD patients with higher SPRR1A expression had poorer overall survival and SPRR1A was identified as an independent unfavorable prognosis factor. In addition, the effects of SPRR1A on lung cancer cells were tested through cellular experiments and the result demonstrated that knockdown of SPRR1A can suppress the proliferation and invasion capacities of tumor cells, while overexpressing SPRR1A exerted opposite effects. Finally, our findings were substantiated by the data obtained from in vivo xenografts using a mice model. In conclusion, LUAD patients with higher SPRR1A expression were more predisposed to poorer clinical outcomes and unfavorable prognoses, indicating the potential role of SPRR1A as a novel clinical biomarker and therapeutic target.

摘要

富含脯氨酸的小蛋白 1A(SPRR1A)在调节鳞状细胞分化中起着关键作用。据报道,SPRR1A 的过表达与某些肿瘤的进展密切相关,如胃癌和结肠癌。然而,SPRR1A 在肺腺癌(LUAD)中的功能尚未阐明。在这里,我们首先检查了 SPRR1A 在 LUAD 组织中的表达模式,结果表明,与正常肺组织相比,LUAD 组织中 SPRR1A 的表达水平显著升高。SPRR1A 的高表达与更大的肿瘤大小密切相关。SPRR1A 表达较高的 LUAD 患者总生存率较差,SPRR1A 被确定为独立的不良预后因素。此外,通过细胞实验测试了 SPRR1A 对肺癌细胞的影响,结果表明,SPRR1A 的敲低可以抑制肿瘤细胞的增殖和侵袭能力,而过表达 SPRR1A 则产生相反的效果。最后,我们使用小鼠模型的体内异种移植实验数据证实了我们的发现。总之,SPRR1A 表达较高的 LUAD 患者更倾向于较差的临床结局和不良预后,表明 SPRR1A 作为一种新的临床生物标志物和治疗靶点具有潜在作用。

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