The LINC00365/SCGB2A1 (Mammaglobin B) Axis Down-Regulates NF-κB Signaling and Is Associated with the Progression of Gastric Cancer

Xiao-Yu Yan; Juan-Juan Zhang; Xin-Ru Zhong; Si-Hang Yu; Long Xu; Rui Tian; Lian-Kun Sun; Jing Su

doi:10.2147/CMAR.S223699

The LINC00365/SCGB2A1 (Mammaglobin B) Axis Down-Regulates NF-κB Signaling and Is Associated with the Progression of Gastric Cancer

Cancer Manag Res. 2020 Jan 28:12:621-631. doi: 10.2147/CMAR.S223699. eCollection 2020.

Authors

Xiao-Yu Yan^#¹, Juan-Juan Zhang^#², Xin-Ru Zhong¹, Si-Hang Yu¹, Long Xu¹, Rui Tian¹, Lian-Kun Sun¹, Jing Su¹

Affiliations

¹ Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, People's Republic of China.
² Department of Basic Medicine, HeXi University, Zhangye, Gansu 734000, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: A lack of early diagnostic biomarkers and therapeutic targets has led to poor prognosis for gastric cancer patients. However, the analysis of cancer-associated genomic data has been shown to be effective in identifying potential markers. Recently, the long non-coding RNA LINC00365 and SCGB2A1 gene (as known as mammaglobin B) were predicted to be co-expressed in gastric cancer based on the Gene Expression Omnibus database. However, their precise role in gastric cancer tumors is still not clear.

Methods: The expressions of LINC00365 and SCGB2A1 in gastric cancer tissues were investigated using qPCR and their expressions were detected in a gastric cancer tissue microarray by in situ hybridization and immunohistochemical staining. The functions of LINC00365 in BGC-823 and MGC-803 gastric cancer cells were tested using the MTT assay, flow cytometry, colony formation assay, EDU staining, immunofluorescence and luciferase assay.

Results: We found that LINC00365 and SCGB2A1 mRNA were both expressed at low levels in 30 cases of gastric cancer. Gastric cancer tissue microarray analysis indicated that LINC00365 and SCGB2A1 were expressed at low levels in tumor tissue, and low expression of both factors correlated with shorter survival time. Functional studies showed that LINC00365 overexpression significantly inhibited gastric cancer cell viability through the impairment of proliferation rather than the promotion of apoptosis. Furthermore, overexpressed LINC00365 upregulated SCGB2A1 in gastric cancer cell lines. Immuno-fluorescence and luciferase assay analysis indicated that LINC00365 overexpression inhibited the NF-κB pro-survival signaling pathway. Consistent with the effects of LINC00365, SCGB2A1 upregulation also reduced cell survival and inactivated NF-κB.

Conclusion: Collectively, our findings revealed that SCGB2A1 may be the target coding protein regulated by LINC00365 in gastric cancer. LINC00365 and SCGB2A1 may function as tumor suppressors and may serve as potential prognostic and therapeutic markers in gastric cancer treatment.

Keywords: LncRNA; NF-κB; gastric cancer; proliferation.

Grants and funding

This work was supported by National Natural Science Foundation of China (81672948, 81772794, 81501982); Jilin Provincial Health Special Project (2018SCZ021); Jilin Provincial Industrial Innovation Project (2018C052-7); Jilin University Bethune Plan B Projects (2015222); and the Fundamental Research Funds for the Central Universities, Jilin University.