Study on the Effects of DCBLD1 on Proliferation Migration and Autophagy in Gastric Cancer Cells and Its Molecular Mechanisms

Expand
  • Department of Gastrointestinal Surgery Affiliated Cancer Hospital of Xinjiang Medical University
    Xinjiang Urumqi 830000, China

Received date: 2025-10-09

  Revised date: 2026-01-02

  Accepted date: 2026-02-06

  Online published: 2026-04-21

Abstract

Objective: To investigate the effects of DCBLD1 on the proliferation migration and autophagy of gastric cancer cells and explore its underlying molecular mechanisms.Methods: Bioinformatics analysis was performed to examine the mRNA expression levels of DCBLD1 in pan-cancer and gastric cancer as well as its predictive value for gastric cancer diagnosis. Western blotting was used to detect DCBLD1 protein expression in gastric cancer cells and normal gastric mucosal cells. DCBLD1 knockdown plasmids were constructed and transfected into AGS and NUGC3 cells followed by Western blotting to assess transfection efficiency and its effects on LC3 and P62 expression. Cell proliferation and migration abilities were evaluated using CCK-8 Transwell and colony formation assays.Results: Bioinformatics analysis revealed that DCBLD1 is highly expressed in multiple cancers. Analysis of 27 paired gastric cancer samples showed that DCBLD1 expression was significantly higher in gastric cancer tissues than in normal tissues. DCBLD1 demonstrated high diagnostic value for gastric cancer. Survival analysis in the Kaplan-Meier Plotter database indicated that gastric cancer patients with high DCBLD1 expression had significantly worse prognosis than those with low expression. Western blot results showed that DCBLD1 protein levels were markedly elevated in gastric cancer cell lines AGS and NUGC3 compared to the normal gastric mucosal cell line GES-1. Knockdown of DCBLD1 increased LC3 expression and decreased P62 expression. CCK-8 assays demonstrated that DCBLD1 knockdown inhibited gastric cancer cell proliferation. Transwell assays revealed that DCBLD1 silencing impaired gastric cancer cell migration. Colony formation assays indicated that DCBLD1 knockdown reduced the clonogenic ability of gastric cancer cells and 3-MA partially reversed the proliferative effects induced by DCBLD1 downregulation.Conclusion: DCBLD1 is highly expressed in gastric cancer cells and promotes their proliferation and migration. This effect may be associated with DCBLD1-mediated inhibition of autophagy.


Cite this article

LAI Bijiang•Wusiman , SONG Dingding, ZHANG Wenbin .

Study on the Effects of DCBLD1 on Proliferation Migration and Autophagy in Gastric Cancer Cells and Its Molecular Mechanisms

[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2026 , 28(3) : 284 -289 . DOI: 10.1009-0959.2025.120016

References

    [1 Bray F Laversanne M Sung H et al. Global cancer statistics 2022 GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countriesJ.CA Cancer J Clin 2024743):229-263.

         2  郑荣寿,陈茹,韩冰峰,等.2022年中国恶性肿瘤流行情况分析[J.中华肿瘤杂志,2024463):221-231.

         3  国家卫生健康委员会医政医管局.胃癌诊疗指南(2022年版)[J.中华消化外科杂志,2022219):1137-1164.

         4  Schmoker AM Ebert AM Ballif BA. The DCBLD receptor family emerging signaling roles in development homeostasis and diseaseJ.Biochem J 20194766):931-950.

         5  Fu LL Yan M Ma MX et al. DCBLD1 overexpression is associated with a poor prognosis in head and neck squamous cell carcinomaJ.Front Immunol 202213939344.

         6  Cardin GB Bernard M Rodier F et al. DCBLD1 is associated with the integrin signaling pathway and has prognostic value in non‑small cell lung and invasive breast carcinomaJ.Sci Rep 2021111):12753.

         7  Xu D Wang Y Liu X et al. Development and clinical validation of a novel 9‑gene prognostic model based on multi‑omics in pancreatic adenocarcinomaJ.Pharmacol Res 2021164105370.

         8  Singletary K Milner J. Diet autophagy and cancer a reviewJ.Cancer Epidemiol Biomarkers Prev 2008177):1596-1610.

         9  Gewirtz DA. The four faces of autophagy implications for cancer therapyJ.Cancer Res 2014743):647-651.

         10 Sooro MA Zhang N Zhang P. Targeting EGFR-mediated autophagy as a potential strategy for cancer therapyJ.Int J Cancer 20181439):2116-2125.

         11 Nawrocki ST Wang W Carew JS. Autophagy new insights into its roles in cancer progression and drug resistanceJ.Cancers 20201210):3005.

         12 张润兵,史婷婷,伍杨,等.自噬介导肝细胞癌耐药的相关机制[J.临床肝胆病杂志,20244011):2315-2319.

         13 郑厚麟,李亚军.自噬与肿瘤干细胞放疗抵抗的研究进展[J. 肿瘤预防与治疗,20213411):1080-1083.

         14 刘芳,鄢玲,陈颖,等.宫颈癌组织中DCBLD1 mRNACKAP2 mRNAEMT相关基因表达及与临床预后的价值研究[J.现代检验医学杂志,2025405):40-45.

         15 Shen Z Li M Zhu H et al. TBP activates DCBLD1 transcription to promote cell cycle progression in cervical cancerJ. Funct Integr Genomics 2024246):221.

         16 赵志,林进权,王春雨,等.铁死亡、自噬及两者关联在胃癌发生中的研究进展[J.陕西医学杂志,2023529):1268-1271.

         17 Lin YLi CMa Y et al. DCBLD1 modulates angiogenesis by regulation of the VEGFR-2 endocytosis in endothelial cellsJ.Arterioscler Thromb Vasc Biol 2025452):198-217.

         18 Wusiman LSong DTulahong A et al. Development and validation of a prognostic prediction model for gastric cancer based on lipophagy-related genesJ.Transl Cancer Res 20251410):6565-6587.

         19 Meng Q Sun H Zhang Y et al. Lactylation stabilizes DCBLD1 activating the pentose phosphate pathway to promote cervical cancer progressionJ.J Exp Clin Cancer Res 2024431):36.

         20 Lai X Fu G Du H et al. Identification of a cancer-associated fibroblast classifier for predicting prognosis and therapeutic response in lung squamous cell carcinomaJ.Medicine Baltimore), 202310238):e35005.

         21 Shen Q Qiu L Zhou Y et al. Pan-cancer analysis of DCBLD1 and its association with the diagnosis immunotherapy and prognosis of cervical cancerJ.Int Immunopharmacol 148114167.

         22 Liu BLin HYu X et al. SNP rs17079281 decreases lung cancer risk through creating an YY1-binding site to suppress DCBLD1 expressionJ.Oncogene 20203920):4092-4102.

Outlines

/