Abstract

Accumulated studies have implicated microRNAs (miRNAs) exert modifying effects on colorectal cancer (CRC). Protein tyrosine phosphatase, receptor type O (PTPRO) has been identified as a tumor suppressor in several kinds of cancer, including CRC. Previously, we have found that exosome-encapsulated miR-6803-5p is increased in CRC. However, the mechanism of miR-6803-5p in CRC is not clear yet. This study is aimed at elucidating the effect of miR-6803-5p in colorectal carcinogenesis. Expression of miR-6803-5p and PTPRO mRNA in peripheral blood mononuclear cells of CRC patients is estimated by real-time PCR. PTPRO protein in CRC cells is detected by western blot. To verify the association of miR-6803-5p with PTPRO, luciferase reporter assay is performed. CCK-8 and EdU assays are conducted to assess cell proliferation. Real-time PCR and ELISA are applied to detect cytokine expression in CRC cells. Cell invasion and migration assays are evaluated by transwell and scratch tests. Immunofluorescence is carried out to determine the activation of NF-κB in HCT116 cells. Negative correlation is demonstrated between miR-6803-5p and PTPRO in CRC. PTPRO is demonstrated to be a direct target of miR-6803-5p. miR-6803-5p can promote cancer cell proliferation and invasion and enhance inflammation through PTPRO/NF-κB axis in CRC, which serves as a useful target for CRC.

Highlights

  • Colorectal cancer (CRC) is a common malignant disease across the world

  • PTPRO is demonstrated to be a direct target of miR-6803-5p. miR-6803-5p can promote cancer cell proliferation and invasion and enhance inflammation through PTPRO/NF-κB axis in CRC, which serves as a useful target for CRC

  • In spite of not coding proteins, dysregulated noncoding RNAs have offered promising strategies for CRC diagnosis and prognosis [9]. microRNAs have 20-24 nucleotides in length. They participate in regulating a variety of genes at the posttranscriptional level by influencing the translation of messenger RNAs [10,11,12]. miRNAs have been established to influence multiple biological activities, including cancer cell proliferation, Mediators of Inflammation

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Summary

Introduction

Colorectal cancer (CRC) is a common malignant disease across the world. It has been well established that environmental factors, genetics, and interactions between them are closely associated with colorectal carcinogenesis [1,2,3]. Receptor type O (PTPRO) belongs to the R3 subtype family of receptor-type protein tyrosine phosphatase It has been suggested as a tumor suppressor for multiple malignancies, such as CRC, hepatocellular carcinoma, and breast cancer [4,5,6]. Many studies have suggested the important role of noncoding RNAs in colorectal carcinogenesis, which are implicated as promising biomarkers in many kinds of malignancies [7, 8]. MicroRNAs (miRNAs) have 20-24 nucleotides in length They participate in regulating a variety of genes at the posttranscriptional level by influencing the translation of messenger RNAs (mRNAs) [10,11,12]. 31 49 invasion, migration, and epithelial mesenchymal transition (EMT) [13,14,15] They act either as oncogenes or tumor suppressors in cancer. The object of the present study is to elucidate the effect of miR-6803-5p and its mechanism in CRC by a series of studies

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