CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma

Abstract

In China, esophageal squamous cell carcinoma (ESCC), capable of direct invasion and early metastasis, exhibits high mortality. Identification of the molecular basis driving ESCC progression and development of new diagnostic biomarkers are urgently needed. Cyclin-dependent kinase inhibitor 3 (CDKN3) performs crucial roles in the modulation of tumor development. The present study aimed to explore the functions and underlying mechanism of CDKN3 in regulating ESCC cell proliferation and invasion. The expression levels of CDKN3 in ESCC cells were evaluated by reverse transcription-quantitative PCR. Cell counting kit-8 and colony forming assays were used to evaluate cell viability. Wound-healing assay was performed to explore cell migration. Transwell invasion analysis was conducted to investigate the invasive capacity of ESCC cells. Protein levels were detected by western blot assay. The results demonstrated that the expression of CDKN3 was significantly upregulated in ESCC tissues, as predicted using the UALCAN and Gene Expression Omnibus databases. PCR and western blot assays confirmed that CDKN3 was upregulated in ESCC cell lines. Functional assays revealed that CDKN3 knockdown with small interfering RNA decreased the ability of ESCC cells to proliferate, invade and migrate and suppressed G1/S transition. Further mechanistic analyses demonstrated that CDKN3 promoted cell proliferation and invasion by activating the AKT signaling pathway in ESCC cells. To the best of our knowledge, the present study is the first to identify the functions of CDKN3 in ESCC and provide evidence that CDKN3 regulates tumor progression by activating the AKT signaling pathway. Therefore, CDKN3 may serve as a potential effective therapeutic target for ESCC treatment.

Integrated Transcriptomics Explored the Cancer-Promoting Genes CDKN3 in Esophageal Squamous Cell Cancer

“…Besides, our immunohistochemical study indicated that there is an abnormal expression of CDKN3 protein in ESCC patients, which preliminarily con rmed its association with the progress of ESCC. Meanwhile, recent studies suggested that CDKN3 is partly responsible for the proliferation, invasion and metastasis of esophageal squamous cell carcinoma via AKT sign pathway dependently or independentl, which also is a corroborative evidence for the reliability of our study [17,18].…”

The role of STEAP1 in the biological behavior of gastric cancer

“…Previous studies have found that the AKT pathway is one of the main signaling pathways in uencing cancer cell proliferation. [24][25][26][27][28][29] Therefore, it was reasonable to consider that STEAP1 can affect cell proliferation via the AKT pathway. Our results also showed that when STEAP1 was downregulated, P-AKT, CDK4, and Cyclin D1 were relatively downregulated, and P27 and P-FoxO1 were upregulated (Fig.…”

Screening and identification of significant genes in esophageal squamous cell carcinoma by bioinformatical analysis

“…CDKN3 is reported to be involved in the occurrence and development of some types of tumors [27,28]. CDKN3 facilitated the promotion of ESCC cell proliferation, invasion and migration by activating the AKT signaling pathway [29]. CDKN3 knockdown significantly inhibited ESCC cell proliferation, migration, and invasion, and suppressed the G1 / S transition of tumor cells, providing a potential target for ESCC treatment [29].…”

“…CDKN3 facilitated the promotion of ESCC cell proliferation, invasion and migration by activating the AKT signaling pathway [29]. CDKN3 knockdown significantly inhibited ESCC cell proliferation, migration, and invasion, and suppressed the G1 / S transition of tumor cells, providing a potential target for ESCC treatment [29]. RAD51-associated protein 1 (RAD51AP1) is an emerging protein that is essential for RAD51-mediated Homologous recombination (HR).…”