Bai Shuya, Chen Wei, Zheng Mengli, Wang Xiju, Peng Wang, Zhao Yuchong, Wang Yun, Xiong Si, Cheng Bin
Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Digestive Endoscopy, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Ann Transl Med. 2021 Sep;9(17):1361. doi: 10.21037/atm-21-1572.
Cancer stemness contributes to hepatocellular carcinoma (HCC) initiation, metastasis, drug resistance, and recurrence. The spindle and kinetochore-associated (SKA) complex has been shown to be involved in tumor progression; however, its effects on cancer stem cell-like properties have not yet been examined. This research sought to study each subunit of the SKA complex in HCC systematically.
Bioinformatic analyses were carried out to examine the expression and clinical data of the SKA complex's each subunit in HCC. The expression of the target genes was detected by quantitative reverse transcription-polymerase chain reaction and Western blot assays. Clone formation and Transwell assays were performed to assess the proliferation and migration abilities of the SKA complex's each subunit. Sphere formation assays and subcutaneous xenograft experiments were performed to investigate the effects of SKA complex subunit 3 (SKA3) on the self-renewal and tumorigenic abilities of HCC.
Each subunit of the SKA complex was highly expressed in HCC, but only SKA complex subunit 1 (SKA1) and SKA3 were associated with the poor overall survival of HCC patients. Additionally, the HCC cells overexpressing SKA3 exhibited increased migration, invasion, proliferation, self-renewal, Sorafenib resistance and tumorigenic abilities. Notch signaling played a vital role in the process by which SKA3 promoted HCC stemness.
SKA3 promotes HCC stem cell-like properties via the Notch signaling pathway. As SKA3 appears to act as a regulator of stemness in HCC, it might be a potential molecular target for HCC.
癌症干性促进肝细胞癌（HCC）的起始、转移、耐药性及复发。纺锤体和动粒相关（SKA）复合体已被证明参与肿瘤进展；然而，其对癌症干细胞样特性的影响尚未得到研究。本研究旨在系统地研究HCC中SKA复合体的各个亚基。
进行生物信息学分析以检测HCC中SKA复合体各亚基的表达及临床数据。通过定量逆转录-聚合酶链反应和蛋白质免疫印迹分析检测靶基因的表达。进行克隆形成和Transwell实验以评估SKA复合体各亚基的增殖和迁移能力。进行成球实验和皮下异种移植实验以研究SKA复合体亚基3（SKA3）对HCC自我更新和致瘤能力的影响。
SKA复合体的每个亚基在HCC中均高表达，但只有SKA复合体亚基1（SKA1）和SKA3与HCC患者的总体生存较差相关。此外，过表达SKA3的HCC细胞表现出迁移、侵袭、增殖、自我更新、索拉非尼耐药性及致瘤能力增强。Notch信号通路在SKA3促进HCC干性的过程中起关键作用。
SKA3通过Notch信号通路促进HCC干细胞样特性。由于SKA3似乎在HCC中作为干性的调节因子发挥作用，它可能是HCC的一个潜在分子靶点。
