The Role of Long Non-Coding RNAs in Thyroid Cancer.
ABSTRACT: Thyroid cancer, the most common endocrine malignancy, has become the most commonly diagnosed malignant solid tumor. Moreover, some cases have poor prognosis, and the survival period is only 3-5 months. Long noncoding RNAs (lncRNAs) are a group of functional RNA molecules more than 200 nucleotides in length that lack the ability to encode protein but participate in all aspects of gene regulation. Functionally, many lncRNAs play essential roles in epigenetic regulation at transcriptional and post-transcriptional levels via various molecular mechanisms. Recent studies have discovered important roles for lncRNAs during the complex process of carcinogenesis in thyroid cancer. In this review, we focus on lncRNAs dysregulated in thyroid cancer and summarize recently reported associations between lncRNAs and thyroid cancer in order to demonstrate the significant value of lncRNAs in diagnosis and treatment.
Project description:CONTEXT:Long noncoding RNAs (lncRNAs) regulate pathological processes, yet their potential roles in papillary thyroid carcinoma (PTC) are poorly understood. OBJECTIVE:To profile transcriptionally dysregulated lncRNAs in PTC and identify lncRNAs associated with clinicopathological characteristics. DESIGN:We performed RNA sequencing of 12 paired PTC tumors and matched noncancerous tissues and correlated the expression of lncRNAs with clinical parameters. The 2 most significantly dysregulated lncRNAs were studied in an Ohio PTC cohort (n = 109) and in PTC data (n = 497) from The Cancer Genome Atlas. SETTING:A combination of laboratory-based studies and computational analysis using clinical data and samples and a publically available database. MAIN OUTCOME MEASURES:Correlation between expression values and clinical parameters. RESULTS:We identified 218 lncRNAs showing differential expression in PTC (fold change ? 2.0, P < .01). Significant correlation was observed between the expression of 2 lncRNAs (XLOC_051122 and XLOC_006074) and 1) lymph node metastasis (N stage) and 2) BRAF(V600E) mutation. Among patients with wild-type BRAF, the expression of these 2 lncRNAs showed significantly higher levels in the patients with lymph node metastasis. In silico analysis of these lncRNAs pinpointed cell movement and cellular growth and proliferation as targeted functions. CONCLUSIONS:Comprehensive expression screening identified 2 novel lncRNAs associated with risk factors of adverse prognosis in PTC patients. These lncRNAs may be novel players in PTC carcinogenesis.
Project description:Recently, a growing number of evidence has revealed that long noncoding RNAs (lncRNAs) act as key regulators in various cellular biologic processes, and dysregulation of lncRNAs involves in tumorigenesis and cancer progression. However, the expression pattern, clinical relevance, and biologic function of most lncRNAs in human thyroid cancer remain unclear. To identify more thyroid-cancer-associated lncRNAs, we analyzed the expression profile of lncRNAs in thyroid cancer tissues and adjacent normal or non-tumor tissues using RNA sequencing data and gene microarray data from The Cancer Genome Atlas and Gene Expression Omnibus. Annotation and analyses of these data revealed that hundreds of lncRNAs are differentially expressed in thyroid cancer tissues when compared with normal tissues. By copy number variation analyses, we identified that some of those dysregulated lncRNAs genome locus are accompanied with the copy number amplification or deletion. Moreover, some lncRNAs expression levels are significantly associated with thyroid cancer patients overall or recurrence-free survival time, such as RUNDC3A-AS1, FOXD2-AS1, PAX8-AS1, and CRYM-AS1. Furthermore, we validated an lncRNA termed LINC00704 in thyroid cancer cells by performing loss of function assays. Downregulation of LINC00704 could significantly impair thyroid cancer cells proliferation, colony formation, inhibit cell-cycle progression and cell invasion, and induce cell apoptosis. Taken together, our findings reveal that lots of lncRNAs are dysregulated and may play critical roles in thyroid cancer, and this study could provide useful resource for identification and investigation of novel lncRNA candidates for thyroid cancer.
Project description:Non-coding RNAs (ncRNAs) play key roles in development, proliferation, differentiation and apoptosis. Altered ncRNA expression is associated with gastric cancer occurrence, invasion, and metastasis. Moreover, aberrant expression of microRNAs (miRNAs) is significantly related to gastric cancer tumor stage, size, differentiation and metastasis. MiRNAs interrupt cellular signaling pathways, inhibit the activity of tumor suppressor genes, and affect the cell cycle in gastric cancer cells. Some miRNAs, including miR-21, miR-106a and miR-421, could be potential markers for the diagnosis of gastric cancer. Long non-coding RNAs (lncRNAs), a new research hotspot among cancer-associated ncRNAs, play important roles in epigenetic, transcriptional and post-transcriptional regulation. Several gastric cancer-associated lncRNAs, such as CCAT1, GACAT1, H19, and SUMO1P3, have been explored. In addition, Piwi-interacting RNAs, another type of small ncRNA that is recognized by gastroenterologists, are involved in gastric carcinogenesis, and piR-651/823 represents an efficient diagnostic biomarker of gastric cancer that can be detected in the blood and gastric juice. Small interfering RNAs also function in post-transcriptional regulation in gastric cancer and might be useful in gastric cancer treatment.
Project description:Recent large-scale transcriptome analyses have revealed that transcription is spread throughout the mammalian genomes, yielding large numbers of transcripts, including long non-coding RNAs (lncRNAs) with little or no protein-coding capacity. Dozens of lncRNAs have been identified as biologically significant. In many cases, lncRNAs act as key molecules in the regulation of processes such as chromatin remodeling, transcription, and post-transcriptional processing. Several lncRNAs (e.g., MALAT1, HOTAIR, and ANRIL) are associated with human diseases, including cancer. Those lncRNAs associated with cancer are often aberrantly expressed. Although the underlying molecular mechanisms by which lncRNAs regulate cancer development are unclear, recent studies have revealed that such aberrant expression of lncRNAs affects the progression of cancers. In this review, we highlight recent findings regarding the roles of lncRNAs in cancer biology.
Project description:Context: Long non-coding RNAs (lncRNAs) regulate pathological processes, yet their potential roles in papillary thyroid carcinoma (PTC) are poorly understood. Objective: To profile transcriptionally dysregulated lncRNAs in PTC and identify lncRNAs associated with clinicopathological characteristics. We performed RNA sequencing of 12 paired PTC tumors and matched noncancerous tissues and correlated the expression of lncRNAs with clinical parameters.
Project description:Whole-transcriptome analyses have revealed that a large proportion of the human genome is transcribed in non-protein-coding transcripts, designated as long non-coding RNAs (lncRNAs). Rather than being "transcriptional noise", increasing evidence indicates that lncRNAs are key players in the regulation of many biological processes, including transcription, post-translational modification and inhibition and chromatin remodeling. Indeed, lncRNAs are widely dysregulated in human cancers, including hepatocellular carcinoma (HCC). Functional studies are beginning to provide insights into the role of oncogenic and tumor suppressive lncRNAs in the regulation of cell proliferation and motility, as well as oncogenic and metastatic potential in HCC. A better understanding of the molecular mechanisms and the complex network of interactions in which lncRNAs are involved could reveal novel diagnostic and prognostic biomarkers. Crucially, it may provide novel therapeutic opportunities to add to the currently limited number of therapeutic options for HCC patients. In this review, we summarize the current status of the field, with a focus on the best characterized dysregulated lncRNAs in HCC.
Project description:Gastric cancer (GC) remains a serious threat to many people, representing the second leading cause of cancer-related death worldwide. The lack of early diagnostic biomarkers, effective prognostic indicators and therapeutic targets all account for the poor prognosis of GC. Therefore, the identification of novel molecular biomarkers for early diagnosis, therapeutic response, and prognosis are urgently needed. High-throughput sequencing has identified a large number of transcribed long non-coding RNAs (lncRNAs) throughout the human genome. Accumulating evidence demonstrates that these lncRNAs play multiple roles in regulating gene expression at the transcriptional, post-transcriptional, and epigenetic levels. Aberrant expression of lncRNAs occurs in various pathological processes, including GC. Many dysregulated lncRNAs in GC have been significantly associated with a larger tumor size, higher degree of tumor invasion, lymph node and distant metastasis, and poorer survival outcome. In this review, we will provide an overview of the pathogenesis of GC, the characteristics and regulatory functions of lncRNAs, and the versatile mechanisms of lncRNAs in GC development, as well as evaluate the translational potential of lncRNAs as novel diagnostic and prognostic biomarkers and therapeutic targets in GC.
Project description:The Human Genome Project revealed that >90% of the human genome was found to transcribe non-coding RNAs, including micro RNAs and long non-coding RNAs (lncRNAs). lncRNAs have been identified to play a crucial role in cancer progression. Thyroid cancer (TC) is a common type of endocrine cancer; however, the functional roles of lncRNAs in TC have yet to be fully elucidated. The present study investigated whether LINC01420 was upregulated in TC tissues, compared with normal thyroid tissues, and the results suggested that LINC01420 may play a regulatory role in TC. Bioinformatics analysis demonstrated that LINC01420 was associated with translation, rRNA processing, mRNA splicing, regulation of transcription, DNA repair and double-strand break repair. Furthermore, the exact role of LINC01420 in TC was explored by performing a loss-of-function assay, which revealed that the knockdown of LINC01420 inhibited TC cell proliferation and cell cycle progression. The findings of the present study provide a novel insight into the molecular mechanisms underlying TC development. Moreover, they suggest that LINC01420 may serve as a potential therapeutic target for the treatment of TC, and that increased LINC01420 expression levels show potential as a prognostic marker for the disease.
Project description:Gastric cancer (GC) is one of the most frequently diagnosed malignant diseases. The molecular mechanisms of metastasis remain unclear. Recently, studies have shown that long non-coding RNAs (lncRNAs) play critical roles in metastasis. Therefore, deeper understanding of this mechanism could provide potential diagnostic tools and therapeutic targets for metastatic GC. This review focuses on dysregulated lncRNAs in GC metastases. Due to the identification of multiple diverse mechanisms involved in GC metastasis, we classified them into seven categories, including lncRNAs related to epithelial-mesenchymal transition, regulation of degradation of extracellular matrix, angiopoiesis, vasculogenic mimicry, and immunologic escape. As the TNM stage is pivotal for evaluating the severity and prognosis of GC patients, we summarize the lncRNAs relevant to lymphatic metastasis, distant metastasis and TNM classification. This review summarizes the lncRNAs related to metastasis, which may provide insight into the mechanisms, and provide potential markers for prognostic prediction and monitoring the relapse of GC.
Project description:BACKGROUND Thyroid cancer is a type of endocrine cancers with rapidly increased incidence. Recent studies have indicated long non-coding RNAs (lncRNAs) played crucial roles in thyroid cancer tumorigenesis and progression. However, the roles of most lncRNAs in thyroid cancer were still unclear. MATERIAL AND METHODS We used TCGA (The Cancer Genome Atlas), GSE50901, GSE29265, and GSE33630 datasets to analyze the expression pattern of ZFAS1 (ZNFX1 antisense RNA 1). The correlation between ZFAS1 and clinicopathological features in thyroid cancer was analyzed. Cell proliferation and cell cycle assays were used to validate the roles of ZFAS1 in thyroid cancer cell lines. DAVID (the database for annotation, visualization and integrated discover) system was used to perform GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. The starBase datasets and Cytoscape was used to perform ceRNA (competitive endogenous RNA) network. RESULTS We demonstrated ZFAS1 was highly expressed in thyroid cancer compared to normal samples. Moreover, upregulation of ZFAS1 was positively correlated with clinicopathological features and poor prognosis in thyroid cancer. Functional validation showed knockdown of ZFAS1 suppressed cell proliferation and cell cycle in thyroid cancer cells. Bioinformatics analysis showed ZFAS1 was associated with translation, rRNA processing, intra-Golgi vesicle-mediated transport, ribosome, and ubiquitin-mediated proteolysis. CONCLUSIONS Our study suggested ZFAS1 could serve as a biomarker for thyroid cancer.