The Clinical Significance of Thyroid Hormone Regulated Long Non-Coding Rnas (lncRNAs) in Human Cancer

The long term goal of my study is to determine the biological significance of the thyroid hormone receptor (TR)-regulated genes. Additionally, the role of TRs during carcinogenesis and clinical significance will be determined. Several studies have proposed that TRs may function as tumor suppressors. These studies suggest that a partial loss of normal TR function due to reduced expression or complete loss of normal TR activity due to mutation and/or aberrant expression provides an opportunity for tumors to proliferate, metastasize and invade. However, increasing evidence supports the notion that wild type TR could play an enhancer role in carcinogenesis under some genetic backgrounds. These observations suggest that TR plays a dual role in human carcinogenesis. Since TR actions are complex and tissue- and time-specific, aberrant expression of the various TR isoforms have different effects and are associated with different types of tumor or stages of development. Therefore, TR role in hepatocellular carcinoma (HCC) is still controversial. Long non-coding RNAs (lncRNAs) regulate gene expression and are involved in diverse biological processes or in carcinogenesis. However, factors that control the expression of lncRNAs remain largely unknown. In the current proposal, we will determine whether lncRNA can be regulated by TRs and its biological significance. Whether TR-regulated lncRNA play any role during carcinogenesis? Five aims are proposed. Specific Aim 1: To identify the TR-regulated lncRNAs, a PCR-based array will be performed and analyzed in HCC cell lines with/without T3 treatment. Alternatively, altering expression of lncRNAs in HCC tissues will be identified. Specific Aim 2: Characterization of the regulation mechanism of lncRNAs those are regulated by T3 in hepatoma cells. Specific Aim 3: Searching for the signaling pathway of candidate lncRNAs or their interacting proteins in hepatoma cells. Specific Aim 4: Functional study of the role of lncRNAs in HCC cells. Specific Aim 5: To determine the expression levels of lncRNAs in clinical specimens. Significance of the proposal: 1) it will offer an opportunity to identify TR regulated lncRNAs in liver cancer and 2) it will provide fundamental knowledge to explore the biological roles of lncRNAs in liver cancer. The lncRNAs newly identified in this study will be used for diagnosis and prognosis, or for the future development of novel therapeutic targets. Finally, the molecular mechanisms of the action of lncRNAs in liver carcinogenesis and cancer progression will be established.

Project ID:PC10401-0611
External Project ID:MOST103-2320-B182-017-MY3