నైరూప్య

Effects of siRNA interference of CDKL1 expression on proliferation and apoptosis of gastric cancer cells

Xiaohong Pan, Yang Yan, Qiken Li, Jiefeng Xu, Yunfeng Zou, Jianbo Zhou, Xiaofeng Huang, Guofeng Chen, Zilong Li

Objective: Cyclin Dependent Kinases (CDKs) play an important role in mediating cell cycle progression, mitosis and proliferation. Cyclin Dependent Kinase Like 1 (CDKL1) has high levels of homology with CDKs and has been shown to be involved in the regulation of cell cycle mediation, although little is known about the exact mechanism. This study used RNA interference (RNAi) approach to downregulate CDKL1 expression in gastric cancer cells, to investigate its role in mediating gastric cancer cell cycle, proliferation, apoptosis as well as its correlation with pathogenesis.

Patients and Methods: Tumor tissues were collected from gastric cancer patients to compare CDKL1 expression across different pathological grades. Its expression was also compared among high differentiated gastric cancer cell line MKN-28 cell, moderate differentiated cell line SGC-7901 cell, low differentiated cell line MGC-803 cell and normal gastric mucosal epithelial cell line GES-1 cell. Cultured MGC-803 cells were transfected with si-CDKL1 to measure cell apoptosis and cycle by flow cytometry and cell proliferation by EdU staining.

Results: Gastric cancer tissues had higher CDKL1 expression than normal mucosal tissues, with higher expression in patients with advanced grades. Gastric cancer cell lines had higher CDKL1 expression than normal cells, with higher expression in those low differentiated cells. siRNA interference downregulated CDKL1 expression in MGC-803 cells, elevated cell apoptosis, induced G0/G1 phase arrest and reduced proliferation potency.

Conclusions: CDKL1 up-regulation is correlated with gastric cancer pathogenesis. CDKL1 downregulation induced gastric cell cycle arresting, inhibited cell proliferation and facilitated cell apoptosis.