Overexpression of LRRC59 Is Associated with Poor Prognosis and Promotes Cell Proliferation and Invasion in Lung Adenocarcinoma
Overexpression of LRRC59 Is Associated with Poor Prognosis and Promotes Cell Proliferation and Invasion in Lung Adenocarcinoma
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DOI：
10.2147/ott.s245336
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发表时间：
2020-01-01
影响因子：
4
通讯作者：
Qian, Jing
中科院分区：
文献类型：
--
作者：
Li, Dong;Xing, Ying;Qian, Jing
目的：LRRC59(富含亮氨酸重复序列的蛋白59)是一种核糖体结合蛋白，也与成纤维细胞生长因子相互作用。有限的研究揭示了LRRC59在乳腺癌侵袭性表型中的可能作用。然而，LRRC59是否参与肺癌的进展尚不清楚。材料和方法：本研究利用在线TCGA生存分析软件(GEPIA2)评估LRRC59基因表达水平对肺癌预后的影响。细胞计数Kit-8法、集落形成实验、细胞周期分析和Transwell实验检测LRRC59在肺癌细胞中的生物学功能。然后收集94例肺腺癌(LUAD)组织，采用组织芯片(TMA)免疫组织化学染色(IHC)检测LRRC59的表达水平。单因素Kaplan-Meier和多因素Cox回归分析评价LRRC59蛋白表达对LUAD患者预后的影响。结果：LRRC59基因表达水平高与肺腺癌患者的预后显著相关，而与肺鳞癌患者的预后无关。ShRNA下调LRRC59基因可明显抑制H1299和A549细胞的增殖和集落形成。LRRC59缺失可诱导A549和H1299细胞发生G1期/S期阻滞。此外，LRRC59的沉默降低了细胞的迁移和侵袭能力。TMA免疫组化结果显示LRRC59在LUAD组织中高表达，且与淋巴结转移密切相关(P
Aim: LRRC59 (leucine-rich repeat-containing protein 59) is a ribosome-binding protein that also interacts with fibroblast growth factors. Limited investigations revealed a possible role of LRRC59 in the aggressive phenotype of breast cancer. However, whether LRRC59 contributes to the progression of lung cancer remains unclear.Materials and Methods: In this study, an online TCGA-based survival analysis software (GEPIA2) was used to estimate the prognostic value of LRRC59 mRNA expression level for lung cancer. Cell Counting Kit-8 assay, colony-forming assay, cell cycle analysis, and transwell assay were used to assess the biological functions of LRRC59 in lung cancer cells. Then, 94 lung adenocarcinoma (LUAD) patient tissues were collected to examine the expression level of LRRC59 by the tissue microarray (TMA)-based immunohistochemistry staining (IHC). Univariate Kaplan-Meier and multivariate Cox regression analyses were performed to evaluate the prognostic value of LRRC59 protein expression in LUAD.Results: Higher mRNA level of LRRC59 was significantly associated with worse survival for lung adenocarcinoma, but not for lung squamous cell carcinoma. Knockdown of LRRC59 by shRNA apparently inhibited cell proliferation and colony formation in both H1299 and A549 cells. The G1/S phase arrest induced by LRRC59 depletion was observed in A549 and H1299 cells. Besides, the silencing of LRRC59 decreased cell migrative and invasive abilities. Moreover, TMA-based IHC showed that LRRC59 was highly expressed in LUAD tissues and closely associated with lymph node metastasis (P