Upregulation of long noncoding RNA LOC100507661 promotes tumor aggressiveness in thyroid cancer
Introduction
Over 90% of the genome consists of noncoding RNAs (ncRNAs) that are transcribed but do not encode proteins (International Human Genome Sequencing Consortium, 2004). These ncRNAs are divided into two major groups based on their size: small ncRNAs and long noncoding RNAs (lncRNAs). Small ncRNAs, which include transcripts such as ribosomal RNAs, transfer RNAs, micro RNAs, and small interfering RNAs, exhibit strong conservation across diverse species and their functions are relatively well known (V. N. Kim et al., 2009). LncRNAs are defined as non-protein coding transcripts longer than 200 nucleotides. In contrast to small ncRNAs, lncRNAs are generally not strongly conserved, and their functions are much less well understood (Derrien et al., 2012). However, several recent studies revealed diverse roles of lncRNAs, including positive or negative effects on transcription and modulation of RNA processing or protein activity; moreover, some lncRNAs serve as precursors for smaller regulatory RNAs (K. C. Wang and Chang, 2011). In addition, lncRNAs are receiving growing attention because they have important functions in tumor biology (Prensner and Chinnaiyan, 2011, Venkatesh et al., 2015).
Although a few lncRNAs such as HOTAIR, H19, and MALAT1 have been investigated in the context of human cancers (Barsyte-Lovejoy et al., 2006, Chunharojrith et al., 2015, Ji et al., 2003, Rinn et al., 2007, Tripathi et al., 2013), fewer studies have focused specifically on the roles of lncRNAs in thyroid cancer. Yoon et al. reported that NAMA (noncoding RNA associated with MAP kinase pathway and growth arrest), which promotes growth arrest, is downregulated in papillary thyroid carcinoma (PTC) harboring BRAF mutations (Yoon et al., 2007). Likewise, PTCSC1 (Papillary Thyroid Carcinoma Susceptibility Candidate 1) in 8q24, PTCSC2 in 9q22, and PTCSC3 in 14q13, which act as tumor suppressors, are downregulated in papillary thyroid carcinoma (He et al., 2009, He et al., 2015, Jendrzejewski et al., 2012, Jendrzejewski et al., 2015). Conversely, BANCR (BRAF-activated lncRNA), which promotes cell proliferation and activates autophagy, is upregulated in PTC (Y. Wang et al., 2014).
Recent advances in next-generation sequencing have discovered various kinds of lncRNAs with potentially critical functions in carcinogenesis in a wide range of human cancers (Prensner and Chinnaiyan, 2011). In this study, we sought to verify lncRNAs described in a previous study and to investigate the biological functions and clinical implications of lncRNAs with potentially important roles in thyroid carcinogenesis.
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Patients and samples
Samples of human thyroid cancer tissue and matched contralateral normal tissue were obtained from 64 patients who underwent thyroidectomy for PTC between April and November 2014 at Yonsei Cancer Center (Seoul, South Korea). All samples were frozen in liquid nitrogen and stored at −80 °C until use. Clinicopathological parameters were retrospectively collected from databases at our institutions. The study protocol was approved by our institutional review board, and informed consent was waived
Identification of lncRNA genes with oncogenic activity in thyroid cancer
To verify newly discovered lncRNAs, we reviewed the results of a previous study that analyzed 2394 tumor SNP arrays from 12 types of cancer in the Tumorscape database created by the Broad Institute (Hu et al., 2014). A total of 1064 lncRNAs were located in 76 regions with focal positive somatic copy number alterations (SCNAs) (i.e., gains in copy number). The top 20 most significant focal alteration peaks contained 56 lncRNAs. We reasoned that lncRNAs in regions with a higher frequency of
Discussion
Thyroid cancer is the most common endocrine malignancy (Davies and Welch, 2006). The prognosis of patients with differentiated thyroid cancer (DTC) is generally favorable because surgery, with or without radioactive iodine therapy, can induce complete remission in most cases (Haugen et al., 2015). However, the current diagnostic and therapeutic strategy is not completely effective in all cases. Although recent advances in our understanding of thyroid carcinogenesis revealed that molecular
Disclosure statement
The authors have nothing to disclose.
Funding
Y.S.J. was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (MEST) (NRF-2015R1D1A1A01058912) and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C2334). J.L. was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (MEST) (NRF-2014R1A1A2059343). D.K. was supported by the
Acknowledgments
The authors are very grateful to Sang Kil Lee and Myoung Hee Kim for helpful advice and suggestions.
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2018, Molecular and Cellular EndocrinologyCitation Excerpt :Additionally, the overexpression of MALAT1 was shown to induce ATC cell proliferation and invasion in vitro through the upregulation of IQGAP1 (Huang et al., 2016). LOC100507661 expression was analyzed in various thyroid cancer cell lines, that include PTC (TPC1, BCPAP), FTC (FTC133), and ATC (C643, 8505C) cells (Kim et al., 2016). PTC and ATC cells displayed LOC100507661 overexpression, with especially high levels in C643 and 8505C.