The promoting effects of GPR176 expression on proliferation, chemoresistance, lipogenesis and invasion of oesophageal cancer

Q: What does the study aim to determine about GPR176 in oesophageal cancer?

It evaluates how GPR176 expression impacts oesophageal cancer clinicopathology and prognosis and seeks to uncover the underlying molecular mechanisms.

Q: How was GPR176 expression measured and linked to clinical features?

RT-PCR and bioinformatic analyses were used to detect GPR176 mRNA expression, then associations were made with clinicopathological stage, histological grade, and clinical outcomes.

Q: What functional effects did GPR176 knockdown have on oesophageal cancer cells?

GPR176 knockdown suppressed proliferation, migration, invasion, apoptosis-related changes, chemoresistance, and lipid droplet formation.

Sep 24, 2026

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GPR176 is evaluated for its role in oesophageal cancer clinicopathology, prognosis, and molecular mechanisms. Bioinformatics and clinical tissue samples assess GPR176 expression and its significance, using phenotypic readouts including proliferation, migration and invasion, apoptosis, and lipid droplet formation. Higher GPR176 mRNA is found in cancer versus normal mucosa and correlates with lower tumor stage and favourable outcomes. GPR176 knockdown suppresses aggressive phenotypes and chemoresistance, while ACC1/ACLY overexpression restores lipid droplet formation and chemoresistance, implicating GPR176-mediated lipogenesis in carcinogenesis and progression.

LanguageEnglish

CategoryHealthcare

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Pages15

Reading Time38 min

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Abstract

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Introduction

Journal of Cancer Research and Clinical Oncology (2023) 149:14641–14655 [https://doi.org/10.1007/s00432-023-05256-2](https://doi.org/10.1007/s00432-023-05256-2) The promoting effects of GPR176 expression on proliferation, chemoresistance, lipogenesis and invasion of oesophageal cancer Wen‑jing Yun1 · Jun Li2 · Nan‑chang Yin3 · Cong‑yu Zhang4 · Zheng‑guo Cui5 · Li Zhang1 · Hua‑chuan Zheng1 Received: 16 July 2023 / Accepted: 7 August 2023 / Published online: 16 August 2023 © The Author(s) 2023 Abstract 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 inoesophageal 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. Keywords Oesophageal cancer · GPR176 · Aggressiveness · Prognosis · Targeted therapy * Hua-chuan Zheng [zheng_huachuan@hotmail.com](zheng_huachuan@hotmail.com) 1 Department of Oncology, The Affiliated Hospital of Chengde Medical University, Chengde 067000, China 2 Department of Thoracic Surgery, Shandong Provincial Hospital, Jinan 250021, China 3 Department of Thoracic Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China 4 Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China 5 Department of Environmental Health, University of Fukui School of Medical Sciences, Fukui 910-1193, Japan Introduction The incidence of oesophageal cancer (OC) is increasing with changes in the environment and the human diet. Adenocarcinoma (Ad) and Squamous cell carcinoma (Sq) are the two most common types of oesophageal cancer, which are caused by distinct genetic alterations that occur in various parts of the oesophagus. Squamous cell carcinoma (Sq) is more common than adenocarcinoma (Ad) . Its risk factors include older age, male sex, smoking, alcohol consumption, exposure to polycyclic aromatic hydrocarbons, gastroesophageal reflux disease, dysplasia and tooth loss. Nonsteroidal anti-inflammatory drugs, vitamins, vegetables, green tea and fruit intake can prevent oesophageal carcinogenesis. Taking into account the patient’s health and the stage of the tumor, endoscopic removal may be used to treat earl

FAQs

What does the study aim to determine about GPR176 in oesophageal cancer?

It evaluates how GPR176 expression impacts oesophageal cancer clinicopathology and prognosis and seeks to uncover the underlying molecular mechanisms.

How was GPR176 expression measured and linked to clinical features?

RT-PCR and bioinformatic analyses were used to detect GPR176 mRNA expression, then associations were made with clinicopathological stage, histological grade, and clinical outcomes.

What functional effects did GPR176 knockdown have on oesophageal cancer cells?

GPR176 knockdown suppressed proliferation, migration, invasion, apoptosis-related changes, chemoresistance, and lipid droplet formation.

Sep 24, 2026

Uploaded by McGucket