RMRP, RMST, FTX and IPW: novel potential long non-coding RNAs in medullary thyroid cancer

Abstract

The relevant role of long non-coding RNAs (lncRNAs) in cancer is currently a matter of increasing interest. Medullary thyroid cancer (MTC) is a rare neuroendocrine tumor (2–5% of all thyroid cancer) derived from the parafollicular C-cells which secrete calcitonin. About 75% of all medullary thyroid cancers are believed to be sporadic medullary thyroid cancer (sMTC), whereas the remaining 25% correspond to inherited cancer syndromes known as Multiple Endocrine Neoplasia type 2 (MEN2). MEN2 syndrome, with autosomal dominant inheritance is caused by germline gain of function mutations in RET proto-oncogene. To date no lncRNA has been associated to MEN2 syndrome and only two articles have been published relating long non-coding RNA (lncRNA) to MTC: the first one linked MALAT1 with sMTC and, in the other, our group determined some new lncRNAs in a small group of sMTC cases in fresh tissue (RMST, FTX, IPW, PRNCR1, ADAMTS9-AS2 and RMRP). The aim of the current study is to validate such novel lncRNAs previously described by our group by using a larger cohort of patients, in order to discern their potential role in the disease. Here we have tested three up-regulated (RMST, FTX, IPW) and one down-regulated (RMRP) lncRNAs in our samples (formalin fixed paraffin embedded tissues from twenty-one MEN2 and ten sMTC patients) by RT-qPCR analysis. The preliminary results reinforce the potential role of RMST, FTX, IPW and RMRP in the pathogenesis of MTC.

The long non-coding RNA rhabdomyosarcoma 2-associated transcript exerts anti-tumor effects on lung adenocarcinoma via ubiquitination of SOX9

“…While RMST has been reported to act as a tumor suppressor in various cancers such as thyroid cancer and head and neck squamous cell carcinomas (18,19), other studies have demonstrated that RMST plays a role as a tumor activator (18). In this current study, RMST expression was downregulated in LUAD tumor tissues compared to normal healthy tissues and high expression of RMST was associated with improved survival in LUAD patients.…”

Bioinformatics Analysis of the Inflammation-Associated lncRNA-mRNA Coexpression Network in Type 2 Diabetes

“…Among the key lncRNAs we identified, FTX, PVT1, and LOXL1-AS1 are currently more studied. FTX is involved in medullary thyroid cancer, osteosarcoma, pancreatic cancer, and other diseases [20][21][22] and plays an important role in the development of inflammation. Research shows that FTX improves the inflammatory response of microglia by competitively binding to miR-382-5p [23].…”

Upregulation of FTX expression is associated with a poor prognosis and contributes to the progression of thyroid cancer

“…Moreover, FTX overexpression promoted tumorigenesis in osteosarcoma by targeting the miR-214-5p/SOX4 signaling axis ( 30 ). Recently, Luzón-Toro et al ( 18 ) reported that FTX was significantly upregulated in sporadic medullary thyroid cancer. The findings of the present study revealed that the expression levels of FTX were upregulated in thyroid cancer tissues and cells, and high FTX expression was associated with lymph node metastasis and clinical stage.…”

“…The lncRNA FTX transcript XIST regulator (FTX), located in the XIST gene locus, has been reported to act as a tumor promoter in various types of cancer, including glioma, lung adenocarcinoma, colorectal cancer, osteosarcoma and gastric cancer, where it was found to be closely associated with a poor prognosis ( 13 – 17 ). In addition, the expression levels of FTX were found to be significantly upregulated in sporadic medullary thyroid cancer ( 18 ). However, to the best of our knowledge, the clinical characteristics, biological functions and underlying mechanism of FTX in thyroid cancer have yet to be determined.…”