miR-26a/b Inhibit Tumor Growth and Angiogenesis by Targeting the HGF-VEGF Axis in Gastric Carcinoma

Abstract

Background/Aims: Abnormal expression of HGF is found in various cancers and correlates with tumor proliferation, metastasis and angiogenesis. However, the regulatory mechanism of the HGF-VEGF axis remains unclear. Methods: The expression characteristic of HGF in human gastric cancer tissues was shown by an immunohistochemistry assay, and the expression levels of target protein were detected by Western blot. The relative levels of miR-26a/b and target mRNA were examined by qRT-PCR. We used bioinformatics tools to search for miRNAs that can potentially target HGF. A luciferase assay was used to confirm direct targeting. Furthermore, the functions of miR-26a/b and HGF were evaluated by cell proliferation and migration assays in vitro and by the mouse xenograft tumor model in vivo. Results: We found that the HGF protein was clearly increased while miR-26a/b were dramatically down-regulated in gastric cancer. miR-26a/b directly bind to the 3'-UTR of HGF mRNA at specific targeting sites. We demonstrated that the repression of the HGF-VEGF pathway by miR-26a/b overexpression suppressed gastric cancer cell proliferation and migration. Furthermore, miR-26a/b also showed an anti-tumor effect in the xenograft mouse model by suppressing tumor growth and angiogenesis. Conclusions: miR-26a/b could suppress tumor tumorigenesis and angiogenesis by targeting the HGF-VEGF axis and could serve as a potential treatment modality for targeted therapy in the clinical treatment of gastric cancer.

Extracellular Vesicles Secreted by Human Urine-Derived Stem Cells Promote Ischemia Repair in a Mouse Model of Hind-Limb Ischemia

“…In this study, we observed that both USCs-EVs and iMSCs-EVs promoted C2C12 myoblast proliferation. Previous studies reported that VEGF, HGF and IGF-1 were not only potential proangiogenic factors but also promoted myoblast proliferation [53][54][55][56][57][58][59]. In the present study, we found that VEGF, HGF and IGF-1 were loaded in the USCs-EVs.…”

Downregulated PITX1 Modulated by MiR-19a-3p Promotes Cell Malignancy and Predicts a Poor Prognosis of Gastric Cancer by Affecting Transcriptionally Activated PDCD5

“…Previous studies showed that miRNAs play vital roles in GC carcinogenesis [32][33][34]. In addition, miR-19b regulates hTERT mRNA expression by targeting PITX1 mRNA in melanoma cells [26], and enhanced miR-886-3p expression regulates cell migration, proliferation, and apoptosis by targeting PITX1 in clear cell renal cell carcinoma [35].…”

The regulatory role of microRNAs in angiogenesis‐related diseases

“…Mechanically, miR‐26a represses VEGF signalling via directly targeting NgBR, and therefore inhibit angiogenesis by performing proliferation, migration and tube formation in HUVECs 118. Furthermore, miR‐26a/b is decreased in gastric cancer and HCC,119, 120 which can inhibit angiogenesis in gastric cancer and reduce the proliferation and migration of gastric cancer via targeting the HGF‐VEGF axis 119. In addition, miR‐26b‐5p is obviously down‐regulated in HCC tissues and HCC cell lines, which represses the apoptosis and tube formation of HCC cells and inhibits angiogenesis via decreasing the expression of VE‐cadherin, Snail and MMP‐2 in vitro and in vivo 120.…”