SKA3/PTTG1/c‐MYC signal loop drives the progression of colorectal cancer

Abstract

To the editorColorectal cancer (CRC) represents a prominent neoplasm globally ranking third in prevalence amongst humans and standing as the second leading cause for cancer-associated fatalities. 1,2 The fundamental molecular mechanisms driving CRC progress remain largely uninvestigated. Spindle and kinetochore-associated complex subunit 3 (SKA3) is an indispensable constituent of the SKA complex that plays a crucial role in stabilising the interaction between kinetochores and microtubules during mitosis. 3,4 Emerging evidence suggests SKA3 is implicated in the progression of various malignancies. 5,6 However, the functional role and mechanism of SKA3 in CRC remain unclear. Here, we demonstrated that SKA3 is pivotal in CRC progress and the SKA3/PTTG1/c-MYC axis could potentially be a latent therapeutic target for CRC.We initially conducted RNA-seq analysis using five pairs of CRC and normal tissues and found that SKA3 was significantly upregulated in CRC tissues (Figure S1A), which was also validated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (GSE83889, GSE106582, and GSE87211) (Figure S1B-E). A Kaplan-Meier analysis in GSE29623 demonstrated patients with high expression levels of SKA3 had unfavorable overall survival (Figure S1F). Western blot assay and immunohistochemical staining (IHC) also confirmed a significant increase of the SKA3 expression in CRC tissues (Figure 1A,B). Compared to normal colorectal cell CCD-18Co, CRC cells displayed elevated levels of SKA3 expression (Figure S1G). In vitro, SKA3 knockdown reduced proliferation, migration and invasion of HCT116 and RKO cells (Figure 1C-G and Figure S2A), whilst SKA3 overexpression leaded to opposite effects (Figure S2A-H). Besides, SKA3 knockdown diminished Proliferating Cell Nuclear Antigen (PCNA) expression, whilst SKA3 overexpression resulted in increased PCNA expression (Figure 1H and Figure S2I). According to the western blot assay of Epithelial Mesenchymal Transition Hao Zhang and Zewen Chang contributed equally to this work.