A subset of microRNAs potentially acts as a convergent hub for upstream transcription factors in cancer cells.
microRNAs (miRNAs) are non-coding short nucleotides that exhibit a unique function as translational suppressors towards a wide realm of mRNAs. To date, a specific set of miRNAs has been characterized as oncogenes and tumor suppressors based on their expression levels and/or target mRNA functions; however, a comprehensive view of the changes in miRNA expression regulated by pivotal cellular signaling mechanisms remains elusive. Here, we aimed to characterize common and unique miRNAs regulated by transcriptional regulators such as oncogenic HRAS, c-Jun and E2F family members (E2F1≈E2F6) in the human cancer cell lines A549 and HeLa. For this purpose, we employed a miRNA microarray and identified several miRNAs that were commonly regulated by transcriptional regulators. Next we tested whether these miRNAs could affect any of the signal pathways by employing luciferase reporters bearing response elements for various cellular signaling pathways. Among those tested, luciferase reporter bearing interferon γ activation site responsive element was solely activated by miR-494, indicating that the overexpression of miR-494 has a limited effect on a specific signal pathway in A549 cells. Taken together, these results suggest that a unique subset of miRNAs could have an integrating effect on upstream pivotal transcriptional regulators influencing decisions regarding proper cellular responses.
Ohdaira
Hiroaki
H
Department of Life Sciences, Faculty of Agriculture, Meiji University, Kawasaki, Kanagawa 214-8571, Japan.
Sasaki
Tomoe
T
Yoshida
Kenichi
K
D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D035683:MicroRNAs; D014157:Transcription Factors