STIL Overexpression Is Associated with Chromosomal Numerical Abnormalities in Non-Small-Cell Lung Carcinoma Through Centrosome Amplification.

IF 2.8 4区医学 Q2 ONCOLOGY Current oncology Pub Date : 2024-12-12 DOI:10.3390/curroncol31120585

Shunsuke Ohtsuka, Hisami Kato, Rei Ishikawa, Hirofumi Watanabe, Ryosuke Miyazaki, Shin-Ya Katsuragi, Katsuhiro Yoshimura, Hidetaka Yamada, Yasuhiro Sakai, Yusuke Inoue, Yusuke Takanashi, Keigo Sekihara, Kazuhito Funai, Haruhiko Sugimura, Kazuya Shinmura

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Abstract

STIL is a regulatory protein essential for centriole biogenesis, and its dysregulation has been implicated in various diseases, including malignancies. However, its role in non-small-cell lung carcinoma (NSCLC) remains unclear. In this study, we examined STIL expression and its potential association with chromosomal numerical abnormalities (CNAs) in NSCLC using The Cancer Genome Atlas (TCGA) dataset, immunohistochemical analysis, and in vitro experiments with NSCLC cell lines designed to overexpress STIL. TCGA data revealed upregulated STIL mRNA expression in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two major subtypes of NSCLC. Immunohistochemical analysis of cases from our hospital (LUAD, n = 268; LUSC, n = 98) revealed STIL protein overexpression. To elucidate the functional role of STIL, an inducible STIL-overexpressing H1299 NSCLC cell line was generated. Overexpression of STIL in these cells promoted centrosome amplification, leading to chromosomal instability. Finally, analysis of arm-level chromosomal copy number alterations from the TCGA dataset revealed that elevated STIL mRNA expression was associated with CNAs in both LUAD and LUSC. These findings suggest that STIL overexpression is associated with CNAs in NSCLC, likely through centrosome amplification, which is linked to chromosomal instability and might represent a potential therapeutic target for NSCLC treatment.

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通过中心体扩增发现非小细胞肺癌中STIL过表达与染色体数量异常相关。

STIL是中心粒生物发生所必需的调节蛋白，其失调与包括恶性肿瘤在内的多种疾病有关。然而，其在非小细胞肺癌（NSCLC）中的作用尚不清楚。在这项研究中，我们利用癌症基因组图谱（TCGA）数据集、免疫组织化学分析和设计过表达STIL的非小细胞肺癌细胞系的体外实验，研究了STIL表达及其与染色体数值异常（CNAs）的潜在关联。TCGA数据显示，STIL mRNA在肺腺癌（LUAD）和肺鳞状细胞癌（LUSC）这两种非小细胞肺癌的主要亚型中表达上调。本院病例免疫组化分析(LUAD, n = 268；LUSC, n = 98)显示STIL蛋白过表达。为了阐明STIL的功能作用，我们构建了一个可诱导的过表达STIL的H1299 NSCLC细胞系。这些细胞中STIL的过度表达促进中心体扩增，导致染色体不稳定。最后，来自TCGA数据集的臂水平染色体拷贝数改变分析显示，LUAD和LUSC中升高的STIL mRNA表达与CNAs相关。这些发现表明，STIL过表达可能通过中心体扩增与非小细胞肺癌中的CNAs相关，这与染色体不稳定性有关，可能是非小细胞肺癌治疗的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current oncology ONCOLOGY-

CiteScore

3.30

自引率

7.70%

发文量

664

审稿时长

1 months

期刊介绍： Current Oncology is a peer-reviewed, Canadian-based and internationally respected journal. Current Oncology represents a multidisciplinary medium encompassing health care workers in the field of cancer therapy in Canada to report upon and to review progress in the management of this disease. We encourage submissions from all fields of cancer medicine, including radiation oncology, surgical oncology, medical oncology, pediatric oncology, pathology, and cancer rehabilitation and survivorship. Articles published in the journal typically contain information that is relevant directly to clinical oncology practice, and have clear potential for application to the current or future practice of cancer medicine.