Endocrine Abstracts

Long non-coding RNAs (lncRNAs) are a class of non-protein coding transcripts longer than 200 nucleotides that regulate complex cellular functions, such as cell growth, differentiation, metabolism, and metastasis. Thyroid hormone (T3) and its receptor (TR) are involved in cancer progression. To identify T3/TR-related lncRNAs that are differentially expressed in HCC, lncRNA expression profile screening was performed using the SYBR Green-based quantitative reverse transcription-PCR (qRT-PCR) array in TR-overexpressing HepG2 cell lines and hepatocellular carcinoma (HCC) specimens. The deregulation of lncRNA expression has been detected in many tumor types, the mechanisms underlying specific involvement of lncRNAs in tumorigenicity remain unclear. Candidate lncRNAs that were simultaneously downregulated by T3/TR and upregulated in HCC were selected for further study, leading to the identification of lncRNA-LOC34 578. LOC34 578 was significantly upregulated in HCC compared to normal tissues. Furthermore, expression of LOC34 578 was significantly positively correlated with overall and recurrence-free survival of HCC patients. Notably, LOC34 578 expression was positively correlated with tumor type, vascular invasion, and pathological stage. These findings suggest that LOC34 578 plays an important regulator in hepatoma. Furthermore, we examined the potential effects of LOC LOC34 578 on hepatoma cell migration and invasion. HCC cells with knockdown of LOC34 578 were further established. Overexpression of LOC34 578 enhanced cell migration ability. On the other hand, knockdown of LOC34 578 significantly suppressed cell migration and invasion, compared with that in cells transfected with control. To further confirm LOC34 578 regulated cell motility, cell migration was measured in LOC34 578-overexpressing cells simultaneously knockdown of LOC34 578. The results indicated LOC34 578 was involved in regulating hepatoma cell motility. To confirm whether the in vitro phenotype of LOC34 578 is reproducible in vivo, the effect of LOC34 578 knockdown on HCC cell tumor formation was examined in nude mice. The knockdown of LOC34 578 reduces tumor growth compared to the control group. Accordingly, LOC34 578 acts as oncogenic lncRNA in HCC. To assess whether LOC34 578 contributes to the activities of EMT, EMT-related genes were examined. The levels of p-STAT3 and MMP2 were lower in LOC34 578-depleted HCC cells relative to their control. E-cadherin, p21, and p27 were higher in knockdown of LOC34 578 cell lines. These findings suggest that LOC34 578 modulated cell migration and cell growth through regulations of EMT-related genes, cell cycle-related markers.