Identification of the Combinatorial Effect of miRNA Family Regulatory Network in Different Growth Patterns of GC

Jia Cheng,Huiqin Zhuo,Lin Wang,Wei Zheng,Xin Chen,Jingjing Hou,Jiabao Zhao,Jianchun Cai

doi:10.1016/j.omto.2020.03.012

Jia Cheng, Huiqin Zhuo + Show 6 more

Open Access

https://doi.org/10.1016/j.omto.2020.03.012

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Abstract

According to the growth pattern, gastric cancer (GC) could be classified into expanding-type GC and infiltrative-type GC (Ming’s classification). The growth pattern of GC is often related to the malignant degree, invasion, metastasis, and other pathological characteristics of tumors. MicroRNAs (miRNAs) play important roles in modulating gene expression during the GC development. In this study, miR-29s were significantly correlated with the gastric carcinogenesis and Ming’s classification. Biological function of miR-29s is most closely related to the pathway of extracellular matrix (ECM)-receptor interaction. ECM structural assembly, cell movement, and cell adhesion are the main functional categories of target genes in this pathway. Among these targets, the COL4A1 gene ranked at the top in the association analysis of combined miR-29s biological function and GC subtype, and miR-29s inhibited its translation by binding to the 3′ UTR region. Infiltrative-type GC cells secrete a higher level of COL4A1 protein than do expanding-type GC cells. The expression of COL4A1 in GC is correlated with clinicopathological features. Downregulation of COL4A1 expression significantly inhibited the migration and invasion of GC cells. High COL4A1 expression was correlated with poor prognosis in survival analysis. The miR-29s regulatory network may affect the development of growth patterns and pathological progress of GC by regulating the function of COL4A1.

Highlights

Gastric cancer (GC) is an important public health problem throughout the world.[1]
This GC classification is not limited by the location and size of tumor growth, which can provide a complete picture of the biological development of GC as the basis of clinical prognosis evaluation combined with tumor-node-metastasis (TNM) staging system.[5,6]
Most Closely Related to the Pathway of Extracellular Matrix (ECM)-Receptor Interaction in Biological Function This study focused on the role of all three members of the miR-29 family in different growth patterns of GC

Summary

Introduction

Gastric cancer (GC) is an important public health problem throughout the world.[1]. There are about 1 million new cases of GC in the world every year, especially in Asia, where the incidence of GC is high.[2]. The overall 5-year survival rate of early stage patients with GC is about 90% after reasonable treatment, while the rate of advanced GC patients is greatly reduced.[3,4] Based on the different patterns of cell growth and infiltration, GC could be accurately classified into expanding-type GC and infiltrative-type GC, i.e., Ming’s classification.[5] Expanding-type GC presents a mass-like expansive growth pattern, often forming numerous discrete tumor nodules in the tumor tissue, while infiltrative-type GC cells show a dispersed infiltration growth, without obvious aggregation.[5] Ming’s classification is based on the structural pattern of tumor tissue, but it combines the biological characteristics of cancer cell growth. This GC classification is not limited by the location and size of tumor growth, which can provide a complete picture of the biological development of GC as the basis of clinical prognosis evaluation combined with tumor-node-metastasis (TNM) staging system.[5,6]

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