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Abstract
Gastric carcinoma is highly prevalent throughout the world. Understanding the pathogenesis of this disease will benefit diagnosis and resolution. Studies show that miRNAs are involved in the tumorigenesis of gastric carcinoma. An initial screening followed by subsequent validation identified that miR-376c is up-regulated in gastric carcinoma tissue and the plasma of patients with the disease. In addition, the urinary level of miR-376c is also significantly increased in gastric carcinoma patients. The plasma miR-376c level was validated as a biomarker for gastric carcinoma, including early stage tumors. The induction of miR-376c was found to enrich the proliferation, migration and anchorage-independent growth of carcinoma cells and, furthermore, the repression of the expression of endogenous miR-376c was able to reduce such oncogenic phenotypes. ARID4A gene is a direct target of miR-376c. Knockdown of endogenous ARID4A increased the oncogenicity of carcinoma cells, while ARID4A was found to be drastically down-regulated in tumor tissue. Thus, expression levels of miR-376c and ARID4A mRNA tended to be opposing in tumor tissue. Our results demonstrate that miR-376c functions by suppressing ARID4A expression, which in turn enhances the oncogenicity of gastric carcinoma cells. It seems likely that the level of miR-376c in plasma and urine could act as invaluable markers for the detection of gastric carcinoma.
Highlights
The International Agency for Research on Cancer (IARC) has reported that gastric carcinoma (GC) to be the fifth most common malignancy worldwide
receiver operating characteristic (ROC) analyses showed that the expression levels of miR376a and miR-376c in the GC tissue had predictive powers of 0.64 and 0.60, respectively, when distinguishing GC tissue from non-cancerous mucosa (NCM) tissue (Fig 1C and 1D) using area under curve (AUC) analysis
It was found that the urinary levels of miR-376c were significantly higher in GC patients compared to the control population (Fig 2C)
Summary
The International Agency for Research on Cancer (IARC) has reported that gastric carcinoma (GC) to be the fifth most common malignancy worldwide. More than 50% of GC cases occur in Eastern Asia, which includes China, Japan, Korea and Taiwan. In 2014, GC ranked as the seventh largest cause of cancer death among all malignancies and sixth highest cause of cancer death among the male population of Taiwan. Surgical resection is the principal treatment modality of GC [1,2,3]. The 5-year survival rate of resectable GC, with three out of five cases being resectable, is about 45% after the curative surgical operation, which implies that about 50% of patients suffer from recurrence of the tumor at a later time.
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