<p>Up-Regulation of MicroRNA-21 Indicates Poor Prognosis and Promotes Cell Proliferation in Esophageal Squamous Cell Carcinoma via Upregulation of lncRNA SNHG1</p>

Abstract

Introduction: MicroRNA-21 (miRNA-21) and lncRNA SNHG1 (small nucleolar RNA host gene 1) are known to be aberrantly upregulated and promote tumor progression in various cancers. Nevertheless, very few studies have determined the roles of tissue and circulating miRNA-21 and SNHG1 in ESCC patients. Particularly, knowledge about the characteristics of miRNA-21 and SNHG1 expression and their correlations with survival rates, as well as their interaction with each other remains inadequate in ESCC. Methods: Thse expression level of miRNA-21 and SNHG1 of tissues, serum and cell lines were detected by qRT-PCR, and the characteristics of their expression and clinicopathology were analyzed. Then, the diagnostic and prognosis value of serum and tissue miRNA-21 and SNHG1 were evaluated, respectively. In addition, the interaction with each other between miRNA-21 and SNHG1, as well as the effect on ESCC cell proliferation were further clarified. Results: The expression level of miRNA-21 and SNHG1 are significantly upregulated in tissues, serum and cell lines of ESCC, and tissue miRNA-21 and SNHG1 significantly correlates with lymph node metastasis, TNM stage, tumor size, and poor overall survival in ESCC patients. The receiver operating characteristic (ROC) curves show that areas under the ROC curve (AUC) for serum miRNA-21 and SNHG1 are 0.928 and 0.850, respectively. Pearson correlation coefficient indicated that the expression levels of miRNA-21 and SNHG1 in frozen cancerous tissues are significantly associated with their respective serum levels. Further, Cox univariate and multivariate analyses reveal that miRNA-21 and SNHG1 are independent prognostic factors for overall survival (OS) and disease-free survival (DFS) in ESCC patients. In addition, our in vitro data revealed a novel regulatory pathway, in which miRNA-21 is probably a unidirectional upstream positive regulator of SNHG1 in ESCC cells, and the interaction between miRNA-21 and SNHG1 plays an important role in the proliferation of ESCC cells. Discussion: In summary, our data show that SNHG1 may be a novel downstream target of miRNA-21 and not vice versa in ESCC cells and contributes significantly toward the proliferation of ESCC cells. These findings suggest that miRNA-21 and SNHG1 may serve as potential diagnostic, prognostic biomarkers and therapeutic targets for ESCC patients.

Tumor-Derived Exosomes in Immunosuppression and Immunotherapy

“…It was shown that serum exosomal miR-320d is a promising noninvasive diagnostic biomarker for distinguishing metastatic from nonmetastatic colorectal cancer [34]. miRNA-21 and lncRNA SNHG1 (small nucleolar RNA host gene 1) may serve as potential diagnostic, prognostic biomarkers and therapeutic targets for esophageal squamous cell carcinoma patients [35]. Exosomal microRNAs have a key role in the tumor microenvironment of breast cancer and may serve as molecular markers [36].…”

The Immunomodulation Potential of Exosomes in Tumor Microenvironment

“…Also, the expression level of circulating exosomal miR-25-3p is also associated with the metastasis of colorectal cancer [ 21 ]. In addition, exosomal miRNAs are also significant in other types of tumors, such as esophageal squamous cell carcinoma [ 22 ] and breast cancer [ 15 ], and serve as molecular biomarkers [ 23 ].…”

Circulating exosomal microRNAs as novel potential detection biomarkers in pancreatic cancer

“…miRNA-21 is upregulated in different types of tumors, such as esophageal squamous cell carcinoma and breast, lung and liver cancer, and targets tumor-suppressive mRNAs (49,50). It was demonstrated that overexpression of serum ex-miRNA-21 was diagnostic of pancreatic ductal adenocarcinoma (51).…”