Abstract

Gastric signet ring cell carcinoma (GSRCC) is a unique pathological type of gastric carcinoma that is extremely invasive and has a poor prognosis after diagnosis. The expression of microRNAs has been closely linked to the carcinogenesis of gastric cancer and has been considered as a powerful prognostic marker. Distinctive expression of miRNAs in GSRCC was investigated in the present study. Samples of GSRCC were compared to that of intestinal gastric adenocarcinoma using Agilent microarray technique, and two differentially expressed miRNAs were identified, hsa-miR-665 and hsa-miR‑95. qRT-PCR verification showed downregulation of both miRNAs in signet ring cell carcinoma and upregulation in gastric adenocarcinoma, which was not consistent with the results obtained by the microarray. Target gene prediction using online databases conferred two strong candidate genes, GLI2 and PLCG1. GO/KO analysis of these two genes showed close correlations with carcinogenesis and chemoresistance. It was concluded that hsa-miR-665 and hsa-miR-95 were downregulated in GSRCC but upregulated in intestinal gastric adenocarcinoma, and the relatively differential expression of the miRNAs negatively controlling their target genes could be closely related to the high invasive metastasis and chemoresistance of GSRCC.

Highlights

  • Gastric cancer is the second most common cancer in the Chinese population and the second leading cause of cancer-Key words: microRNA, gastric signet ring cell carcinoma, gastric adenocarcinoma related death worldwide

  • In order to conduct a comparative analysis with intestinal-type gastric adenocarcinoma (IGA), we adopted microarray technology to identify the unique miRNAs and mRNAs that are related to the biological features of gastric signet ring cell carcinoma (GSRCC)

  • Expressed miRNAs were identified from the GSRCC (T1/P1) and IGA (T2/P2) groups using the Agilent mRNA chip

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Summary

Introduction

We speculated that the invasiveness and resistance of GSRCC are likely due to the unique miRNA and mRNA regulation. In order to conduct a comparative analysis with intestinal-type gastric adenocarcinoma (IGA), we adopted microarray technology to identify the unique miRNAs and mRNAs that are related to the biological features of GSRCC. This should provide significant understanding of the mechanisms involved in GSRCC metastasis and chemotherapy resistance. Expressed miRNAs in GSRCC were thoroughly studied to determine the biological function of the targeted mRNAs in the occurrence of cancer. The present study aimed to compare the miRNA profile of IGA and GSRCC tissues and their targeted mRNAs

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Lauren P: The two histological main types of gastric carcinoma
19. Shenouda SK and Alahari SK: MicroRNA function in cancer
51. Skalsky RL and Cullen BR
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