p53 represses c-Myc through induction of the tumor suppressor miR-145

miR-145 induces caspase-dependent and -independent cell death in urothelial cancer cell lines with targeting of an expression signature present in Ta bladder tumors

“…The majority of mRNAs (85%) and miRNAs other than miR-145 (>95%) remained unchanged ( Figure 6a and data not shown). The reported miR-145 targets, insulin receptor substrate-1, and MYC that have been speculated to influence the growth inhibitory effect of miR-145 (Shi et al, 2007;Sachdeva et al, 2009) were not expressed or in fact induced rather than repressed, respectively, and, therefore, unlikely to account for the phenotype observed in our model system. As individual miRNAs are estimated to target hundreds of mRNAs, we hypothesized that the phenotypic effects of miR-145 may be a consequence of the combined alteration of numerous targets instead of a single target gene and that it may result from both primary, secondary, and subsequent regulatory effects.…”

“…p53 response elements identified in the putative promoter region of mir145 suggest that upon p53 inactivation, the transcription of miR-145 may be reduced (Sachdeva et al, 2009). However, p53 is seldomly inactivated in Ta tumors (Mitra et al, 2007) and thus cannot account for the early loss of miR-145.…”

“…Furthermore, studies have shown that miR-145 reduces cell viability in colon and cervical cancer cell lines after prolonged exposure (Shi et al, 2007;Schepeler et al, 2008;Wang et al, 2008). Finally, the expression of miR-145 has been shown to be induced by p53 (Sachdeva et al, 2009) and regulated by an enhancer element activated by SRF and Nkx-2 transcription factors (Cordes et al, 2009).…”

Is microRNA-143 really a turncoat of tumor suppressor microRNA in hepatitis B virus–related hepatocellular carcinoma? #

“…First, we believe that these questions are the precise questions that we were interested in answering from the very beginning of our study. Due to the word limits and in the interest of preparing a succinct manuscript, we did experiments to demonstrate that miR-143 is directly transcribed by the transcription factor NF-B in accordance with the study of Li et al 5 From a methodological perspective, it would certainly be more convincing if we applied additional assays, such as a promoter-reporter assay or electrophoretic mobility-shift assay. Moreover, we certainly believe that there may be different indirect regulatory forces acting on hepatitis B x antigen (HBx), NF-B, and miR-143 due to the multiple roles of NF-B and HBx in HCC development.…”

“…It functions as a tumor suppressor in carcinogenesis. 5 Therefore, what are the authors' opinions on the role of mir-143, a partner of mir145, in HBV-related HCC: does it act as tumor suppressor microRNA or oncomir?…”