Research Paper Volume 15, Issue 9 pp 3394—3409

GRB10 is a novel factor associated with gastric cancer proliferation and prognosis

Li-Li Ren1, *, , Zhi-Wen Wang2, *, , Ren Sen3, , Zhou-Tong Dai2,4, , Xing-Hua Liao2, , Li-Juan Shen5, ,

  • 1 School of Food and Drug, Shenzhen Polytechnic, Guangdong 518055, China
  • 2 Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Hubei 430081, China
  • 3 Clinical Academy, Changsha Health Vocational College, Hunan 410100, China
  • 4 Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
  • 5 Longgang District People's Hospital of Shenzhen, Guangdong 518172, China
* Equal contribution

Received: November 9, 2022       Accepted: February 27, 2023       Published: March 23, 2023      

https://doi.org/10.18632/aging.204603
How to Cite

Copyright: © 2023 Ren et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

GRB10 and its family members GRB7 and GRB14 were important adaptor proteins. They regulated many cellular functions by interacting with various tyrosine kinase receptors and other phosphorus-containing amino acid proteins. More and more studies have shown that the abnormal expression of GRB10 is closely related to the occurrence and development of cancer. In our current research, expression data for 33 cancers from the TCGA database was downloaded for analysis. It was found that GRB10 was up-regulated in cholangiocarcinoma, colon adenocarcinoma, head and neck squamous carcinoma, renal chromophobe, clear renal carcinoma, hepatocellular carcinoma, lung adenocarcinoma, lung squamous carcinoma, gastric adenocarcinoma and thyroid carcinoma. Especially in gastric cancer, the high GRB10 expression was closely associated with poorer overall survival. Further research showed that the knockdown of GRB10 inhibited proliferation and migration ability in gastric cancer. Also, there was a potential binding site for miR-379-5p on the 3′UTR of GRB10. Overexpression of miR-379-5p in gastric cancer cells reduced GRB10-regulated gastric cancer proliferation and migration capacity. In addition, we found that tumor growth was slower in a mice xenograft model with knock down of GRB10 expression. These findings suggested that miR-379-5p suppresses gastric cancer development by downregulating GRB10 expression. Therefore, miR-379-5p and GRB10 were expected to be potential targets for the treatment of gastric cancer.

Abbreviations

ACC: adrenocortical carcinoma; BLCA: bladder urothelial carcinoma; BRCA: breast invasive carcinoma; CESC: cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL: cholangiocarcinoma; COAD: colon adenocarcinoma; DLBC: lymphoid neoplasm diffuse large B-cell lymphoma; ESCA: esophageal carcinoma; GBM: glioblastoma multiforme; HNSC: head and neck squamous cell carcinoma; KAP1: KRAB-associated protein-1; KICH: kidney chromophobe; KIPAN: pan-kidney cohort; KIRC: kidney renal clear cell carcinoma; KIRP: kidney renal papillary cell carcinoma; KRAB-ZNF: Krüppel-associated box domain zinc finger; LGG: brain lower grade glioma; LIHC: liver hepatocellular carcinoma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; OV: ovarian serous cystadenocarcinoma; PAAD: pancreatic adenocarcinoma; PCPG: pheochromocytoma and paraganglioma; PRAD: prostate adenocarcinoma; READ: rectum adenocarcinoma; SARC: sarcoma; STAD: stomach adenocarcinoma; STES: stomach and esophageal carcinoma; TCGA: The Cancer Genome Atlas; TGCT: testicular germ cell tumors; THCA: thyroid carcinoma; THYM: thymoma; TRIM28: Tripartite-motif containing 28; UCEC: uterine corpus endometrial carcinoma; UCS: uterine carcinosarcoma; UVM: uveal melanoma.