ISSN : 2146-3123
E-ISSN : 2146-3131

Knockdown of Serum- and Glucocorticoid-Regulated Kinase 1 Enhances Cisplatin Sensitivity of Gastric Cancer Through Suppressing the Nuclear Factor Kappa-B Signaling Pathway
Jishui Zhang1, Wenhao Lv1, Yagang Liu1, Weihua Fu2, Baosheng Chen1, Qiutong Ma1, Xin Gao3, Xiuxia Cui4
1The Second Department of General Surgery, Cangzhou Central Hospital, Cangzhou, Hebei, China
2Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
3Department of Radiotherapy, Cangzhou Central Hospital, Cangzhou, Hebei, China
4Department of Nuclear Medicine, Cangzhou Central Hospital, Cangzhou, Hebei, China
DOI : 10.5152/balkanmedj.2021.21114
Pages : 331-340

Background: Previous studies have published the promoting effect of serum and glucocorticoid-regulated kinase 1 (SGK1) in various malignant tumors. However, whether SGK1 promotes gastric cancer remains a mystery.
Aims: To clarify the function of SGK1 in gastric cancer and its potential regulatory mechanism.
Study Design: Cell culture study.
Methods: The SGK1-silenced model was generated in two gastric cancer cell lines and further evaluated their malignant behavior and susceptibility to cisplatin. The interaction between miR-15a-5p and SGK1 was evaluated by the luciferase reporter assay. The knockdown efficiency of SGK1 was confirmed by RT- qPCR and Western blot assays. Cell proliferation rate was assessed with CCK-8 assay, and flow cytometry was used to determine cell cycle progression and apoptosis.
Results: Western blot data displayed an elevated level of SGK1 in gastric cancer cell lines. Functionally, SGK1 deficiency suppressed gastric cancer cell proliferation (P < .01) by acting on cell-cycle progression. Moreover, SGK1 deficiency suppressed cell invasion and migration of gastric cancer cells (P < .01). Further, the silencing of SGK1 obviously suppressed cell proliferation and induced apoptosis of the cells after cisplatin treatment (P < .01), indicating that SGK1 deficiency facilitated the chemosensitivity of these 2 gastric cancer cell lines to cisplatin. Mechanically, downregulation of SGK1 repressed the cytoplasm- to-nucleus translocation of NF-κB p65. Interestingly, we found that miR-15a-5p binds to the 3'UTR of SGK1, which was confirmed using luciferase activity assay (P < .05). Moreover, the data suggested that SGK1 reversed the suppression effect of miR-15a-5p on gastric cancer cell migration (P < .01).
Conclusion: Loss of SGK1 suppresses the malignant behavior of gastric cancer cells and increases cisplatin sensitivity by restraining the NF-κB signaling pathway. Moreover, SGK1 may exert an inhibitory effect in gastric cancer by being targeted by miR-15a-5p. Therefore, SGK1 may be a prospective target for future gastric cancer therapy.

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