SEC61G participates in endoplasmic reticulum stress by interacting with CREB3 to promote the malignant progression of lung adenocarcinoma

Zhang,Qian; Guo,Zhongliang

doi:10.3892/ol.2022.13316

SEC61G participates in endoplasmic reticulum stress by interacting with CREB3 to promote the malignant progression of lung adenocarcinoma

Authors:
- Qian Zhang
- Zhongliang Guo
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Affiliations: Shanghai East Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
Published online on: May 30, 2022 https://doi.org/10.3892/ol.2022.13316
Article Number: 233
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

As the most common type of lung cancer, lung adenocarcinoma (LUAD) poses a great threat to human health worldwide and severely compromises the quality of life of the patients. The present study aimed to explore the potential pathogenesis of LUAD. Reverse transcription‑quantitative PCR and western blotting were applied to measure the expression levels of SEC61 translocon subunit γ (SEC61G) and cyclic AMP‑responsive element‑binding protein 3 (CREB3). Western blotting was also used to determine the expression of endoplasmic reticulum (ER) stress‑, apoptosis‑ and migration‑related proteins. Cell Counting Kit‑8, colony formation, TUNEL, wound healing and Transwell assays were used, respectively, to determine the viability, proliferation, apoptosis, migration and invasion of LUAD A549 cells. The association between SEC61G and CREB3 was verified by co‑immunoprecipitation assay. The results revealed that SEC61G was upregulated in A549 cells and its downregulation could activate ER stress. It was also found that silencing SEC61G inhibited the malignant development of LUAD through ER stress. In addition, SEC61G was verified to participate in ER stress in LUAD via CREB3 and silencing SEC61G exerted inhibitory effects on the malignant progression of LUAD by regulating CREB3. In summary, SEC61G participated in ER stress and its knockdown exerted inhibitory effects on A549 cells via regulating CREB3, which suggests that SEC61G may be a potential therapy for patients with LUAD.

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1	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2019. CA Cancer J Clin. 69:7–34. 2019. View Article : Google Scholar : PubMed/NCBI
3	Abe Y and Tanaka N: The hedgehog signaling networks in lung cancer: The mechanisms and roles in tumor progression and implications for cancer therapy. Biomed Res Int. 2016:79692862016. View Article : Google Scholar : PubMed/NCBI
4	Zhao Y, Varn FS, Cai G, Xiao F, Amos CI and Cheng C: A P53-deficiency gene signature predicts recurrence risk of patients with early-stage lung adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 27:86–95. 2018. View Article : Google Scholar : PubMed/NCBI
5	Greenfield JJ and High S: The Sec61 complex is located in both the ER and the ER-Golgi intermediate compartment. J Cell Sci. 112:1477–1486. 1999. View Article : Google Scholar : PubMed/NCBI
6	Liang L, Huang Q, Gan M, Jiang L, Yan H, Lin Z, Zhu H, Wang R and Hu K: High SEC61G expression predicts poor prognosis in patients with head and neck squamous cell carcinomas. J Cancer. 12:3887–3899. 2021. View Article : Google Scholar : PubMed/NCBI
7	Oakes SA and Papa FR: The role of endoplasmic reticulum stress in human pathology. Annu Rev Pathol. 10:173–194. 2015. View Article : Google Scholar : PubMed/NCBI
8	Liu Y, Ji W, Shergalis A, Xu J, Delaney AM, Calcaterra A, Pal A, Ljungman M, Neamati N and Rehemtulla A: Activation of the unfolded protein response via inhibition of protein disulfide isomerase decreases the capacity for DNA repair to sensitize glioblastoma to radiotherapy. Cancer Res. 79:2923–2932. 2019. View Article : Google Scholar : PubMed/NCBI
9	Gao H, Niu W, He Z, Gao C, Peng C and Niu J: SEC61G plays an oncogenic role in hepatocellular carcinoma cells. Cell Cycle. 19:3348–3361. 2020. View Article : Google Scholar : PubMed/NCBI
10	Meng H, Jiang X, Wang J, Sang Z, Guo L, Yin G and Wang Y: SEC61G is upregulated and required for tumor progression in human kidney cancer. Mol Med Rep. 23:4272021. View Article : Google Scholar : PubMed/NCBI
11	Sampieri L, Di Giusto P and Alvarez C: CREB3 transcription factors: ER-Golgi stress transducers as hubs for cellular homeostasis. Front Cell Dev Biol. 7:1232019. View Article : Google Scholar : PubMed/NCBI
12	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
13	Li W, Gao LN, Song PP and You CG: Development and validation of a RNA binding protein-associated prognostic model for lung adenocarcinoma. Aging (Albany NY). 12:3558–3573. 2020. View Article : Google Scholar : PubMed/NCBI
14	Zhang C, Zhang Z, Zhang G, Zhang Z, Luo Y, Wang F, Wang S, Che Y, Zeng Q, Sun N and He J: Clinical significance and inflammatory landscapes of a novel recurrence-associated immune signature in early-stage lung adenocarcinoma. Cancer Lett. 479:31–41. 2020. View Article : Google Scholar : PubMed/NCBI
15	Shi Y, Liang Y, Wang W and Zhang G: SEC61G identified as a prognostic biomarker of head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol. 279:2039–2048. 2022. View Article : Google Scholar : PubMed/NCBI
16	Sheu JJ, Hua CH, Wan L, Lin YJ, Lai MT, Tseng HC, Jinawath N, Tsai MH, Chang NW, Lin CF, et al: Functional genomic analysis identified epidermal growth factor receptor activation as the most common genetic event in oral squamous cell carcinoma. Cancer Res. 69:2568–2576. 2009. View Article : Google Scholar : PubMed/NCBI
17	Oh-Hashi K, Soga A, Naruse Y, Takahashi K, Kiuchi K and Hirata Y: Elucidating post-translational regulation of mouse CREB3 in Neuro2a cells. Mol Cell Biochem. 448:287–297. 2018. View Article : Google Scholar : PubMed/NCBI
18	Hu Y, Chu L, Liu J, Yu L, Song SB, Yang H and Han F: Knockdown of CREB3 activates endoplasmic reticulum stress and induces apoptosis in glioblastoma. Aging (Albany NY). 11:8156–8168. 2019. View Article : Google Scholar : PubMed/NCBI
19	Penney J, Taylor T, MacLusky N and Lu R: LUMAN/CREB3 plays a dual role in stress responses as a cofactor of the glucocorticoid receptor and a regulator of secretion. Front Mol Neurosci. 11:3522018. View Article : Google Scholar : PubMed/NCBI
20	Penney J, Mendell A, Zeng M, Tran K, Lymer J, Turner PV, Choleris E, MacLusky N and Lu R: LUMAN/CREB3 is a key regulator of glucocorticoid-mediated stress responses. Mol Cell Endocrinol. 439:95–104. 2017. View Article : Google Scholar : PubMed/NCBI