CKS2 Promotes the Growth in Non-Small-Cell Lung Cancer by Downregulating Cyclin-Dependent Kinase Inhibitor

Abstract

<b><i>Introduction/Objective:</i></b> This study aimed to explore the expression of cyclin-dependent kinase subunit 2 (CKS2) in tissues and cells in non-small-cell lung cancer (NSCLC) and the function mechanism of CKS2 in NSCLC cell growth and tumorigensis. <b><i>Methods:</i></b> After transfecting NCI-H2170 cells with short-hair RNA (shRNA), an shCKS2 gene-silencing model was established. The cells were divided into a shRNA group and shNC group. For overexpression cell lines, we used the same method to establish the NCI-H2170-CKS2 cell lines. Cell Count Kit-8 assay and colony formation assay were used to determine cell viability and cell growth, respectively. Propidium iodide staining was used to determine cell cycle progression. The mRNA expression of CKS2 and protein expression of CKS2, p21, p53, and PTEN were determined by RT-qPCR and Western blotting, respectively. The expression of CKS2, p53, and Ki67 in tissues was determined by immunohistochemical stain. The in vivo tumorigenesis assays were used to determine the ability of CKS2 in tumor growth. <b><i>Results:</i></b> The results of RT-qPCR and Western blotting assay revealed that CKS2 upregulated expression in NSCLC tissues and cells. The results of the CCK-8 assay revealed that the shRNA group exhibited significantly lower cell viability and foci formation than the empty plasmid group, while CKS2 overexpression induces cell growth and cell cycle progression. The result of nude mice suggested that CKS2 knockdown expression suppressed tumorigenesis in the in vivo animal model. <b><i>Conclusions:</i></b> Our study suggests that CKS2 could be a biomarker in the progression and prognosis of NSCLC.

Global trends and hotspots in Cyclin-dependent Kinase Subunit 2 research from 1999 to 2022: A bibliometric and visualized analysis

“…[29] In lung cancer,CKS2 could promote growth and cell cycle by downregulating Cell Cycle-Dependent Kinase Inhibitor(CKI), including p53, p21, and PTEN. [30] CKS2 may be a therapeutic target for the treatment of a variety of cancers.…”

Cyclin-Dependent Kinase Subunit 2 (CKS2) as a Prognostic Marker for Stages I–III Invasive Non-Mucinous Lung Adenocarcinoma and Its Role in Affecting Drug Sensitivity

“…In contrast to other studies on the expression of CKS2 in LUAD [ 38 , 39 , 40 ], the primary focus of our research was on invasive lung adenocarcinoma, the most common type of LUAD. Additionally, we investigated in depth the expression of CKS2 in various histological subtypes of invasive lung adenocarcinoma and identified the roles of CKS2 in affecting the drug sensitivity of LUAD tumor cells to carboplatin and paclitaxel.…”

Bioinformatics-based identification of key genes and pathways associated with colorectal cancer diagnosis, treatment, and prognosis

“…[21] Numerous studies showed that dysregulation of CKS2 may contribute to the growth and metastasis of tumors in breast cancer, ovarian cancer, hepatocellular carcinoma, non-small-cell lung cancer, and colorectal cancer. [22][23][24][25][26] CCNA2, CCNB1, CDK1, and CKS2 are key molecules involved in the cell cycle and play a crucial role in tumorigenesis and cancer progression. Their significance for the diagnosis and treatment of colorectal cancer is also well known.…”