Department of Oncology and Haematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, Zhejiang, PR China.
Department of General Surgery, Breast and Thyroid Unit, Tribhuvan University Teaching Hospital, Kathmandu, Nepal.
Clin Breast Cancer. 2024 Jul;24(5):e333-e349.e1. doi: 10.1016/j.clbc.2024.02.011. Epub 2024 Mar 6.
Female breast cancer has become the world's most common malignant tumor, displacing lung malignancy, and the incidence of malignant tumors has increased continuously in recent decades. However, the underlying molecular mechanisms of breast tumorigenesis have not been fully elucidated. By consulting the literature, we discovered that the TIMM8A gene could affect oxidative stress and apoptosis in patients with Mohr-Tranebjærg syndrome. However, the biological function of TIMM8A has yet to be explored.
We investigated the expression level of TIMM8A via bioinformatic analysis and performed immunohistochemistry, diagnostic value, immune infiltration, functional enrichment, and survival analyses. Nonetheless, in vitro, additional experiments were performed. We explored whether TIMM8A expression was greater in breast tumors than in nearby normal tissues through qRT‒PCR. The expression of TIMM8A was knocked down by siRNA. Then, we conducted proliferation tests (CCK-8 experiment and colony formation) and Transwell assays (migration and invasion assays) to determine the specific biological functions of TIMM8A in the MDA-MB-231 and BT-549 cell lines.
Tumor samples exhibited higher TIMM8A expression and exon expression, whereas normal tissues had higher TIMM8A methylation. The expression level of TIMM8A was linked to immune infiltration and survival, making it a valuable prognostic indicator and effective diagnostic tool. Functional enrichment analysis of TIMM8A indicated potential pathways through which it may play a role. In vitro experiments demonstrated that suppressing TIMM8A significantly inhibited the viability, colony formation, migration, and invasion of breast carcinoma cell lines.
This study revealed that TIMM8A is an oncogene and is critical for the tumorigenesis of breast carcinoma.
女性乳腺癌已成为全球最常见的恶性肿瘤，取代了肺癌恶性肿瘤，且近几十年来恶性肿瘤的发病率持续增加。然而，乳腺癌发生的潜在分子机制尚未完全阐明。通过查阅文献，我们发现 TIMM8A 基因可影响 Mohr-Tranebjærg 综合征患者的氧化应激和细胞凋亡。然而，TIMM8A 的生物学功能尚未得到探索。
我们通过生物信息学分析研究 TIMM8A 的表达水平，并进行免疫组织化学、诊断价值、免疫浸润、功能富集和生存分析。然而，我们还进行了更多的体外实验。我们通过 qRT-PCR 探讨 TIMM8A 在乳腺癌组织中的表达是否高于邻近正常组织。通过 siRNA 敲低 TIMM8A 的表达。然后，我们进行增殖试验（CCK-8 实验和集落形成实验）和 Transwell 分析（迁移和侵袭实验），以确定 TIMM8A 在 MDA-MB-231 和 BT-549 细胞系中的具体生物学功能。
肿瘤样本中 TIMM8A 的表达和外显子表达较高，而正常组织中 TIMM8A 的甲基化程度较高。TIMM8A 的表达水平与免疫浸润和生存相关，使其成为有价值的预后指标和有效的诊断工具。TIMM8A 的功能富集分析表明了其可能发挥作用的潜在途径。体外实验表明，抑制 TIMM8A 显著抑制乳腺癌细胞系的活力、集落形成、迁移和侵袭。
本研究揭示了 TIMM8A 是一种癌基因，对乳腺癌的发生至关重要。
