Molecular Role of SGK3 Gene in Promoting the Progression of Non-small Cell Lung Cancer

Miao Li; Qingyu Yang; Yan Rui

doi:10.54097/g937df95

Authors

Miao Li
Qingyu Yang
Yan Rui

DOI:

https://doi.org/10.54097/g937df95

Keywords:

Non-small Cell Lung Cancer, SGK3, Immunohistochemistry, Lung Cancer

Abstract

Objective: To investigate the role of SGK3 in the progression of non-small cell lung cancer and investigate its effect on cell growth using lung cancer cell lines. Method: A retrospective analysis was conducted on 134 non-small cell lung cancer patients diagnosed in our hospital from January 2014 to December 2018, including 83 cases of adenocarcinoma and 51 cases of squamous cell carcinoma. Immunohistochemical staining was used to divide lung cancer specimens from patients into SGK3 negative and positive groups, and the correlation between SGK3 expression and clinical data was analyzed. Subsequently, cellular level experimental validation was carried out using the A549 lung cancer cell line. Result: Clinical data confirmed that SGK3 was significantly overexpressed in lung cancer tissue (P<0.05), and the difference in its expression level was not related to factors such as age and gender of SGK3 patients, but only showed a significant correlation with TNM staging and lymph node metastasis (P<0.05). In addition, through CCK-8 cell growth rate measurement experiments and cell scratch and invasion experiments, it is speculated that the above clinical findings may be due to the pro cancer effect of SGK3. Conclusion: SGK3 is highly expressed in cancer tissues of non-small cell lung cancer patients. SGK3 promotes lung cancer cell growth and division, suggesting that this regulatory factor may be involved in the occurrence and development of non-small cell lung cancer.

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References

Yu Q, Luo J, Zhang J, et al. Oxymatrine inhibits the development of non-small cell lung cancer through miR-367-3p upregulation and target gene SGK3 downregulation [J]. Am J Transl Res, 2020, 12(9): 5538-50.

Zarogoulidis K, Zarogoulidis P, Darwiche K, et al. Treatment of non-small cell lung cancer (NSCLC) [J]. J Thorac Dis, 2013, 5 Suppl 4(Suppl 4): S389-96.

Wang Y, Zhou D, Chen S. SGK3 Is an Androgen-Inducible Kinase Promoting Prostate Cancer Cell Proliferation Through Activation of p70 S6 Kinase and Up-Regulation of Cyclin D1 [J]. Molecular Endocrinology, 2014, 28(6): 935-48.

He P, Lee S-J, Lin S, et al. Serum-and glucocorticoid-induced kinase 3 in recycling endosomes mediates acute activation of Na+/H+ exchanger NHE3 by glucocorticoids [J]. Molecular biology of the cell, 2011, 22(20): 3812-25.

Yao L-J, Mccormick J A, Wang J, et al. Novel role for SGK3 in glucose homeostasis revealed in SGK3/Akt2 double-null mice [J]. Molecular Endocrinology, 2011, 25(12): 2106-18.

Bruhn M A, Pearson R B, Hannan R D, et al. Second AKT: the rise of SGK in cancer signalling [J]. Growth factors, 2010, 28(6): 394-408.

Zheng Yaya, Yang Zeyu, Liu Mengmeng, etc Expression and significance of SGK3 in non-small cell lung cancer tissue [J]. Journal of Shenyang Medical College, 2022, 24 (02): 137-139+160.

Alam M, Hasan G M, Eldin S M, et al. Investigating regulated signaling pathways in therapeutic targeting of non-small cell lung carcinoma [J]. Biomedicine & Pharmacotherapy, 2023, 161,114452.

Bruhn M A, Pearson R B, Hannan R D, et al. AKT-independent PI3-K signaling in cancer – emerging role for SGK3 [J]. Cancer Management and Research, 2013, 5(null): 281-92.

Zheng Yaya Expression and significance of SGK3 in non-small cell lung cancer [D], 2021.

Tessier M, Woodgett J R. Role of the Phox homology domain and phosphorylation in activation of serum and glucocorticoid-regulated kinase-3 [J]. J Biol Chem, 2006, 281(33): 78-89.

Arcaro A, Guerreiro A S. The phosphoinositide 3-kinase pathway in human cancer: genetic alterations and therapeutic implications [J]. Curr Genomics, 2007, 8(5): 271-306.

Li Y, Corradetti M N, Inoki K, et al. TSC2: filling the GAP in the mTOR signaling pathway [J]. Trends in biochemical sciences, 2004, 29(1): 32-8.

Basnet R, Basnet B B. Mechanisms of Activation and Key Roles of SGK3 Under Physiological Conditions and in Prostate and Breast Cancer [J]. Current Signal Transduction Therapy, 2021, 16(2): 122-8.

Wang Y, Zhou D, Chen S. SGK3 is an androgen-inducible kinase promoting prostate cancer cell proliferation through activation of p70 S6 kinase and up-regulation of cyclin D1 [J]. Mol Endocrinol, 2014, 28(6): 35-48.

Lee E, Mckean-Cowdin R, Ma H, et al. Characteristics of triple-negative breast cancer in patients with a BRCA1 mutation: results from a population-based study of young women [J]. J Clin Oncol, 2011, 29(33): 73-80.

Fedele C G, Ooms L M, Ho M, et al. Inositol polyphosphate 4-phosphatase II regulates PI3K/Akt signaling and is lost in human basal-like breast cancers [J]. Proc Natl Acad Sci U S A, 2010, 107(51): 1-6.

Fan X-R, Zhang Z-Y, Wang R-H, et al. MiR-376a functions as tumor suppressor by targeting SGK3 in renal cell carcinoma [J]. European Review for Medical & Pharmacological Sciences, 2019, 23(9).

Jin H, Yang L, Wang L, et al. INPP4B promotes cell survival via SGK3 activation in NPM1-mutated leukemia [J]. Journal of Experimental & Clinical Cancer Research, 2018, 37:1-15.