MicroRNA miR-29a inhibits colon cancer progression by downregulating B7-H3 expression: potential molecular targets for colon cancer therapy

Abstract

BackgroudMiR-29a belongs to one of the subtypes of miRNAs known as non-coding single-stranded RNAs, and is preferentially expressed in normal tissues. B7-H3, a member of the B7/CD28 immunoglobulin superfamily, was shown to be overexpressed in several solid malignant tumors, including colon cancer. In addition, it is associated with tumor progression and poor prognosis.MethodsWe used immunohistochemical and western blotting to assess B7-H3 protein expression levels in colon cancer and adjacent normal tissues, and then compared their relationships with clinicopathological factors. Quantitative real time reverse transcription PCR was used to assess B7-H3 and miRNA-29a mRNA expression levels, and then their relationship and clinical significance were evaluated. In addition, colon cancer Caco-2 cells, which constitutively overexpress B7-H3, were transfected with lentivirus particles for miR-29a upregulation. Invasion and migration assays were carried out in vitro along with the establishment of a subcutaneous xenograft model in vivo to determine the role of miRNA-29a in colon cancer progression.ResultsThe B7-H3 protein showed elevated expression in colon carcinoma, and was relevant to TNM staging, lymph node metastasis and reduced survival. Meanwhile, miR-29a was preferentially expressed in normal colon tissues while B7-H3 transcript levels had no marked differences between tumor and normal tissue specimens. In vitro, miR-29a upregulation resulted in reduced B7-H3 expression. Furthermore, miR-29a upregulation reduced the invasive and migratory abilities of colon carcinoma cells. In animal models, upregulation of miR-29a slowed down the growth of subcutaneous xenotransplanted tumors, and resulted in prolonged survival time.ConclusionMiR-29a downregulates B7-H3 expression and accordingly inhibits colon cancer progression, invasion and migration, indicating miR-29a and B7-H3 might represent novel molecular targets for advanced immunotherapy in colon cancer.