Regulation and Expression of Micronrna by Thyroid Hormone and Its Clinic Significance

Thyroid hormone (T3) regulates growth, development and differentiation. These activities are mediated by the nuclear thyroid hormone receptors (TRs), which belong to the steroid/thyroid hormone receptor superfamily of ligand-dependent transcription factors. Previous study indicated that T3 might play a critical role in repressing the proliferation of hepatoma cells. Recently, microRNAs (miRNA) are found as a small, short, endogenously expressed non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Mounting evidence not only indicates that aberrant expression of miRNAs is involved in the development of cancer, but also suggests that they can act either as oncogenes or tumor suppressor genes. Lately study even point at miRNA can induce apoptosis and a cell cycle arrest in the G1-phase, thereby suppressing tumor cell proliferation. Since both of T3/TR signaling and miRNAs are involved in tumorigenesis, it is interested to know whether the TR, a transcription factor, could regulate the expression of miRNAs in hepatoma cells, even further cause the effect of cell growth. Supposing miRNAs can be regulated by T3, the next work is to identify which genes are targeted by those T3-regulated miRNAs. To study the relationship between miRNA and T3, a TRα1 overexpressing hepatoma cell line (HepG2-TRα1) was used. Furthermore, quantitative reverse transcription polymerase chain reaction (Q-RT-PCR) was performed to detect the regulation and expression of miRNA by T3. According to the preliminary data, several miRNAs expression was up- or down-regulated by T3 treatment. These T3-regulated miRNAs will be verified by Northern blot or Dot blot. The function of TR-regulated miRNA will be studied. Subsequently, the genes which are targeted by miRNAs will also be identified by oligomicroarray. Finally, in the light of function of TR-regulated miRNA and which affect gene expression profile, the role of miRNA in hepatocellular carcinoma (HCC) will be established.

Project ID:PA9706-0972
External Project ID:NSC97-2321-B182-001