Yan Xiao-Yu, Zhang Juan-Juan, Zhong Xin-Ru, Yu Si-Hang, Xu Long, Tian Rui, Sun Lian-Kun, Su Jing
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.
Department of Basic Medicine, HeXi University, Zhangye, Gansu 734000, People's Republic of China.
Cancer Manag Res. 2020 Jan 28;12:621-631. doi: 10.2147/CMAR.S223699. eCollection 2020.
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 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.
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.
We found that LINC00365 and 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.
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.
缺乏早期诊断生物标志物和治疗靶点导致胃癌患者预后不良。然而，癌症相关基因组数据分析已被证明在识别潜在标志物方面是有效的。最近，基于基因表达综合数据库预测长链非编码RNA LINC00365和SCGB2A1基因（也称为乳腺珠蛋白B）在胃癌中共同表达。然而，它们在胃癌肿瘤中的精确作用仍不清楚。
采用qPCR研究LINC00365和SCGB2A1在胃癌组织中的表达，并通过原位杂交和免疫组化染色在胃癌组织芯片中检测它们的表达。使用MTT法、流式细胞术、集落形成试验、EDU染色、免疫荧光和荧光素酶试验检测LINC00365在BGC-823和MGC-803胃癌细胞中的功能。
我们发现LINC00365和SCGB2A1 mRNA在30例胃癌中均低表达。胃癌组织芯片分析表明，LINC00365和SCGB2A1在肿瘤组织中低表达，且两者低表达均与较短的生存时间相关。功能研究表明，LINC00365过表达通过损害增殖而非促进凋亡显著抑制胃癌细胞活力。此外，过表达的LINC00365上调胃癌细胞系中的SCGB2A1。免疫荧光和荧光素酶试验分析表明，LINC00365过表达抑制NF-κB促生存信号通路。与LINC00365的作用一致，SCGB2A1上调也降低细胞存活并使NF-κB失活。
总体而言，我们的研究结果表明，SCGB2A1可能是LINC00365在胃癌中调控的靶编码蛋白。LINC00365和SCGB2A1可能作为肿瘤抑制因子，在胃癌治疗中可能作为潜在的预后和治疗标志物。
