Search

Tumor angiogenesis is a crucial step in the further growth and metastasis of solid tumors. However, its regulatory mechanism remains unclear. Here, we showed that TARBP2, an RNA‐binding protein, played a role in promoting tumor‐induced angiogenesis both in vitro and in vivo through degrading the mRNAs of antiangiogenic factors, including thrombospondin1/2 (THBS1/2), tissue inhibitor of metalloproteinases 1 (TIMP1), and serpin family F member 1 (SERPINF1), by targeting their 3′untranslated regions (3′UTRs). Overexpression of TARBP2 promotes tumor cell–induced angiogenesis, while its knockdown inhibits tumor angiogenesis. Clinical cohort analysis revealed that high expression level of TARBP2 was associated with poor survival of lung cancer and breast cancer patients. Mechanistically, TARBP2 physically interacts with the stem‐loop structure located in the 3′UTR of antiangiogenic transcripts, leading to mRNA destabilization by the dsRNA‐binding domains 1/2 (dsRBDs1/2). Notably, the expression level of TARBP2 in human tumor tissue is negatively correlated with the expression of antiangiogenic factors, including THBS1/2, and brain‐specific angiogenesis inhibitor 1 (BAI1). Moreover, TARBP2 expression is strongly associated with tumor angiogenesis in a group of human lung cancer samples. Collectively, our results highlight that TARBP2 is a novel tumor angiogenesis regulator that could promote tumor angiogenesis by selectively downregulating antiangiogenic gene expression. [ABSTRACT FROM AUTHOR]

Despite a library full of literature on miRNA biology, core issues relating to miRNA target detection, biological effect, and mode of action remain controversial. This essay proposes that the predominant mechanism of direct miRNA action is translational inhibition, whereas the bulk of miRNA effects are mRNA based. It explores several issues confounding miRNA target detection, and discusses their impact on the dominance of miRNA seed dogma and the exploration of non-canonical binding sites. Finally, it makes comparisons between miRNA target prediction and transcription factor binding prediction, and questions the value of characterizing miRNA binding sites based on which miRNA nucleotides are paired with an mRNA. [ABSTRACT FROM AUTHOR]

The fungal elicitors, a xylanase from Trichoderma viride and an extract from the cell wall of Phytophthora infestans, are shown to cause a rapid reduction of the mRNA levels of various cell cycle-related genes, including MAP kinase genes and cyclin genes, in cultured tobacco cells ( Nicotiana tabacum cv. Xanthi, line XD6S). Pharmacological analyses suggest that the elicitor-induced decrease in B1-type cyclin (Nicta; CycB1;3) and A1-type cyclin (Nicta; CycA1;1) mRNAs may be due to transcriptional repression, and that in D3-type cyclin (Nicta; CycD3;2) mRNA due to destabilization of the mRNA molecule itself. The activity of protein kinases is required for both the activation of defence genes and the repression of cyclin genes. The transcriptional activity of the promoter of the B1-class cyclin gene decreases upon elicitor treatment. The transactivation activity of NtmybA2, a tobacco Myb transcription activator for the M phase-specific cis-acting elements in the promoter of the B-type cyclin gene, is inhibited by elicitor treatment. In addition, the mRNA levels of NtmybA2 and two other related genes, NtmybA1 and NtmybB, decrease in response to the elicitor. Finally, we discuss a negative cross-talk between signal transduction pathways for growth and defence responses, which might be important for adaptation to environmental stress by potential pathogens. [ABSTRACT FROM AUTHOR]