MicroRNA-885-3p inhibits the growth of HT-29 colon cancer cell xenografts by disrupting angiogenesis via targeting BMPR1A and blocking BMP/Smad/Id1 signaling

Abstract

The previous studies in this lab discovered that microRNA-885-3p (miR-885-3p) was regulated by a sulfated polysaccharide that bound to bone morphogenetic protein receptor, type IA (BMPR1A) to inhibit angiogenesis. However, its specific role and its mechanism of action in tumor cells have not been elucidated. We show that miR-885-3p markedly suppresses angiogenesis in vitro and in vivo. MiR-885-3p inhibits Smad1/5/8 phosphorylation and downregulates DNA-binding protein inhibitor ID-1 (Id1), a proangiogenic factor, by targeting BMPR1A, leading to impaired angiogenesis. Overexpression or silencing of BMPR1A affects angiogenesis in a Smad/Id1-dependent manner. We further show that miR-885-3p impairs the growth of HT-29 colon cancer cell xenografts in nude mice by suppressing angiogenesis through disruption of BMPR1A and Smad/Id1 signaling. These results support a novel role for miR-885-3p in tumor angiogenesis by targeting BMPR1A, which regulates a proangiogenic factor, and provide new evidence that targeting miRNAs might be an effective therapeutic strategy for improving colon cancer treatment.

microRNA-374a suppresses colon cancer progression by directly reducing CCND1 to inactivate the PI3K/AKT pathway

“…In recent studies, microRNA deregulations have been frequently observed and induce the pathogenesis of human colorectal cancers [1–6]. miR-374a, located on chromosome Xq13.2, promotes or suppresses development of human cancer according to different studies.…”

MicroRNA-93-5p may participate in the formation of morphine tolerance in bone cancer pain mouse model by targeting Smad5

“…Using certain biology software, we find that Smad5 is also a target gene of miR-93. As suggested, bone morphogenetic protein (BMP)/Smad signaling pathway promote the vascular development [16]. As a key mediator of BMP/Smad pathway, Smad5 can act as a target of microRNA to suppress the endothelial development and thereby the angiogenesis, a must for tumor progression and tumor metastases [17, 18].…”

Overexpression of Transforming Acidic Coiled Coil‑Containing Protein 3 Reflects Malignant Characteristics and Poor Prognosis of Glioma

“…A total of 10 miRNAs were negatively correlated with TACC3 expression and qualified as having a binding site within the TACC3 mRNA 3′ untraslational region. Some of these miRNAs, such as miR-1224-5p [27], miR-30e-3p [28], miR-488-3p [29], miR-491-5p [30], miR-940 [31] and miR-885-3p [32], are proven as tumor suppressors for various cancers. In the CGGA miRNA dataset, these TACC3 negatively associated miRNAs were significantly downregulated in high grade glioma (except for miR-330-3p, p = 0.4164) (Figure S5).…”