Shanghai Lung Tumor Clinical Medicine Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, P. R. China.
Department of Stomatology, Ordos central hospital, Ordos, Inner Mongolia, 017000, P. R. China.
Cell Death Dis. 2022 Aug 6;13(8):685. doi: 10.1038/s41419-022-05140-w.
In view of the important roles played by Kinetochore proteins in mitosis, we believed that they may contribute to the development and progression of human cancers, which has been reported recently elsewhere. Kinetochore-associated 1 (KNTC1) participates in the segregation of sister chromatids during mitosis, the effects of which on non-small-cell lung cancer (NSCLC) remain unclear. Here, we sought to identify the biological significance of KNTC1 in NSCLC. KNTC1 protein expression in NSCLC tissues was investigated by immunohistochemistry. Lentivirus delivered short hairpin RNA (shRNA) was utilized to establish KNTC1 silence NSCLC cell lines. The effects of KNTC1 depletion on NSCLC cell proliferation, migration, apoptosis, and tumor formation were analyzed by MTT assay, wound-healing assay, transwell assay, flow cytometry assay, and in nude mouse models in vivo. After KNTC1 reduction, NSCLC cell viability, proliferation, migration, and invasion were restrained. A xenograft tumor model was also provided to demonstrate the inhibited tumorigenesis in NSCLC. In addition, the downstream mechanism analysis indicated that KNTC1 depletion was positively associated with PSMB8. The findings of the present study suggested that KNTC1 may have a pivotal role in mediating NSCLC progression and may act as a novel therapeutic target for NSCLC.
鉴于动粒蛋白在有丝分裂中的重要作用，我们认为它们可能有助于人类癌症的发展和进展，这在最近的其他地方也有报道。动粒相关蛋白 1（KNTC1）参与有丝分裂过程中姐妹染色单体的分离，其对非小细胞肺癌（NSCLC）的影响尚不清楚。在这里，我们试图确定 KNTC1 在 NSCLC 中的生物学意义。通过免疫组织化学检测 NSCLC 组织中 KNTC1 蛋白的表达。利用慢病毒递送短发夹 RNA（shRNA）建立 KNTC1 沉默 NSCLC 细胞系。通过 MTT 检测、划痕愈合检测、Transwell 检测、流式细胞术检测和体内裸鼠模型分析 KNTC1 耗竭对 NSCLC 细胞增殖、迁移、凋亡和肿瘤形成的影响。在 KNTC1 减少后，NSCLC 细胞活力、增殖、迁移和侵袭受到抑制。还提供了一个异种移植肿瘤模型来证明 NSCLC 中肿瘤发生的抑制。此外，下游机制分析表明 KNTC1 的缺失与 PSMB8 呈正相关。本研究的结果表明，KNTC1 可能在介导 NSCLC 进展中起关键作用，并可能成为 NSCLC 的一种新的治疗靶点。
