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PURPOSE

As a member of the G-protein-coupled receptor 1 family, the G-protein-coupled receptor 176 (GPR176) gene encodes a glycosylated protein made up of 515 amino acids. The current study was performed to evaluate the impact of GPR176 on the clinicopathology and prognosis of oesophageal cancer, as well as uncover its molecular mechanisms.

METHODS

Bioinformatics and clinical tissue samples were used to detect the expression and clinicopathological significance of GPR176 in oesophageal cancer. The expression, proliferation, migration and invasion, apoptosis and lipid droplet formation of GPR176 gene in oesophageal cancer were performed as phenotypic readouts.

RESULTS

Here, RT-PCR and bioinformatic analyses revealed that GPR176 mRNA expression was significantly higher in oesophageal cancer than in normal mucosa (p < 0.05). GPR176 mRNA expression was associated with low weight and BMI, low T stage, low N and clinicopathological stage, low histological grade and favourable clinical outcome of oesophageal cancer (p < 0.05). The differential genes of GPR176 mRNA were involved in protein digestion and absorption, extracellular matrix constituent, endoplasmic reticulum lumen, among others (p < 0.05). GPR176-related genes were classified as being involved in oxidoreductase activity, actin and myosin complexes, lipid localisation and transport, among others (p < 0.05). GPR176 knockdown suppressed proliferation, anti-apoptotic and anti-pyroptotic properties, migration, invasion, chemoresistance and lipid droplet formation in oesophageal cancer cells (p < 0.05), while ACC1 and ACLY overexpression reversed the inhibitory effects of GPR176 silencing on lipid droplet formation and chemoresistance.

CONCLUSION

These findings indicated that upregulated expression of GPR176 might be involved in oesophageal carcinogenesis and subsequent progression, aggressiveness, and induced chemoresistance by ACC1- and ACLY-mediated lipogenesis and lipid droplet assembly.

PURPOSE

METHODS

RESULTS

CONCLUSION

目的

作为 G 蛋白偶联受体 1 家族的成员，G 蛋白偶联受体 176（GPR176）基因编码一种由 515 个氨基酸组成的糖基化蛋白。本研究旨在评估 GPR176 对食管癌的临床病理和预后的影响，并揭示其分子机制。

方法

使用生物信息学和临床组织样本检测 GPR176 在食管癌中的表达及其临床病理意义。将 GPR176 基因在食管癌中的表达、增殖、迁移和侵袭、凋亡和脂滴形成作为表型读出。

结果

RT-PCR 和生物信息学分析显示，GPR176 mRNA 在食管癌中的表达明显高于正常黏膜（p<0.05）。GPR176 mRNA 表达与体重和 BMI 低、T 分期低、N 分期和临床病理分期低、组织学分级低以及食管癌的良好临床结局相关（p<0.05）。GPR176 mRNA 的差异表达基因参与蛋白质消化和吸收、细胞外基质成分、内质网腔等（p<0.05）。GPR176 相关基因被归类为涉及氧化还原酶活性、肌动蛋白和肌球蛋白复合物、脂质定位和运输等（p<0.05）。GPR176 敲低抑制了食管癌细胞的增殖、抗凋亡和抗焦亡特性、迁移、侵袭、化疗耐药性和脂滴形成（p<0.05），而 ACC1 和 ACLY 的过表达逆转了 GPR176 沉默对脂滴形成和化疗耐药性的抑制作用。