Further experiments demonstrated that the MYEOV ceRNA sequestered miR-30c-2-3p from binding its targets TGFBR2 and USP15 mRNAs, which in turn leading to constitutive activation of TGF-β signaling and tumor progression in NSCLC.
Our findings elucidate diverse hypoxia-regulated pathways including EZH2-mediated hypermethylation and miR-93-induced silencing contribute to attenuation of TGFBR2 expression and promote cancer progression in prostate cancer.
Similarly, TGFβ1 and TGFβ3, but not TGFβ2, showed higher expression levels in advanced lymph node-positive and metastatic tumors, suggesting different roles for the different isoforms in tumor progression and the metastatic process, while in the least aggressive molecular subtype (luminal A), expression of the three TGFβ isoforms significantly correlated with expression of both TGFβ receptors, such correlation only occurred between TGFβ1 and TGFβ3 and the TGFβ type II receptor (TβRII) in the highly aggressive basal-like subtype.
Moreover, ZEB1 and TGFBR2, which are essential components of the TGF-b signaling pathway, were identified as direct targets of miR-655, suggesting that the activation of the TGF-b-ZEB1-E-cadherin axis by aberrant downregulation of miR-655 may accelerate cancer progression.
In conclusion, in lung cancer cells, SCUBE3 could serve as an endogenous autocrine and paracrine ligand of TGF-β type II receptor, which could regulate TGF-β receptor signaling and modulate EMT and cancer progression.
Our results contribute to the understanding of how the TGFBR2 and BAX gene mutations contribute to tumor progression in the mutator phenotype pathway for MSI colorectal cancers.