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      Long non-coding RNA FEZF1-AS1 facilitates cell proliferation and migration in colorectal carcinoma

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          Abstract

          Long non-coding RNAs (lncRNA) have been shown to play important roles in the development and progression of cancer. Here, we discovered a novel long noncoding RNA (lncRNA) FEZF1 antisense RNA1 ( FEZF1-AS1) is markedly upregulated in human primary colorectal carcinoma (CRC) and associated with CRC metastasis and poor prognosis. Moreover, the downregulation of FEZF1-AS1 expression significantly inhibited the CRC cells proliferation, migration and invasiveness, suppressed S-phase entry in vitro, and repressed tumor growth and metastasis in vivo. In contrast, overexpression of FEZF1-AS1 could promote the aggressive behaviors of CRC cells. We further discovered that the downregulation of FEZF1-AS1 reduced its sense-cognate gene FEZF1 mRNA and protein expression in CRC cells. There was a positive correlation between FEZF1-AS1 and FEZF1 expression in CRC. Moreover, FEZF1 knockdown also significantly suppressed CRC cell proliferation, migration, and invasion. Our findings indicate that the dysregulation of FEZF1-AS1 participates in colorectal tumorigenesis and progression, which might be achieved, at least in part, through FEZF1 induction.

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          Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells.

          Sabine Loewer, Moran Cabili, Mitchell Guttman … (2010)
          The conversion of lineage-committed cells to induced pluripotent stem cells (iPSCs) by reprogramming is accompanied by a global remodeling of the epigenome, resulting in altered patterns of gene expression. Here we characterize the transcriptional reorganization of large intergenic non-coding RNAs (lincRNAs) that occurs upon derivation of human iPSCs and identify numerous lincRNAs whose expression is linked to pluripotency. Among these, we defined ten lincRNAs whose expression was elevated in iPSCs compared with embryonic stem cells, suggesting that their activation may promote the emergence of iPSCs. Supporting this, our results indicate that these lincRNAs are direct targets of key pluripotency transcription factors. Using loss-of-function and gain-of-function approaches, we found that one such lincRNA (lincRNA-RoR) modulates reprogramming, thus providing a first demonstration for critical functions of lincRNAs in the derivation of pluripotent stem cells.
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            Long intergenic noncoding RNAs: new links in cancer progression.

            Miao-Chih Tsai, Robert C Spitale, Howard Y. Chang (2011)
            The process of cancer metastasis involves a series of sequential and complex steps. Here we give a perspective on recent results regarding noncoding transcription in cancer progression, focusing on the emerging role of long intergenic noncoding RNAs (lincRNAs). LincRNAs target chromatin modification complexes or RNA-binding proteins to alter gene expression programs. Similarly to miRNAs, lincRNAs exhibit distinct gene expression patterns in primary tumors and metastases. We discuss how lincRNAs can be used for cancer diagnosis and prognosis and serve as potential therapeutic targets. © 2011 AACR.
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              The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion.

              Divya Khaitan, Marcel E Dinger, Joseph Mazar … (2011)
              The identification of cancer-associated long noncoding RNAs (lncRNAs) and the investigation of their molecular and biological functions are important to understand the molecular biology of cancer and its progression. Although the functions of lncRNAs and the mechanisms regulating their expression are largely unknown, recent studies are beginning to unravel their importance in human health and disease. Here, we report that a number of lncRNAs are differentially expressed in melanoma cell lines in comparison to melanocytes and keratinocyte controls. One of these lncRNAs, SPRY4-IT1 (GenBank accession ID AK024556), is derived from an intron of the SPRY4 gene and is predicted to contain several long hairpins in its secondary structure. RNA-FISH analysis showed that SPRY4-IT1 is predominantly localized in the cytoplasm of melanoma cells, and SPRY4-IT1 RNAi knockdown results in defects in cell growth, differentiation, and higher rates of apoptosis in melanoma cell lines. Differential expression of both SPRY4 and SPRY4-IT1 was also detected in vivo, in 30 distinct patient samples, classified as primary in situ, regional metastatic, distant metastatic, and nodal metastatic melanoma. The elevated expression of SPRY4-IT1 in melanoma cells compared to melanocytes, its accumulation in cell cytoplasm, and effects on cell dynamics, including increased rate of wound closure on SPRY4-IT1 overexpression, suggest that the higher expression of SPRY4-IT1 may have an important role in the molecular etiology of human melanoma.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Oncotarget
                Journal ID (iso-abbrev): Oncotarget
                Journal ID (publisher-id): Oncotarget
                Journal ID (publisher-id): ImpactJ
                Title: Oncotarget
                Publisher: Impact Journals LLC
                ISSN (Electronic): 1949-2553
                Publication date Collection: 8 March 2016
                Publication date (Electronic): 3 February 2016
                Volume: 7
                Issue: 10
                Pages: 11271-11283
                Affiliations
                1 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
                2 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
                3 Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
                Author notes
                Correspondence to: Jun Zhou, jzhou16@ 123456163.com
                Article
                Publisher ID: 7168
                DOI: 10.18632/oncotarget.7168
                PMC ID: 4905472
                PubMed ID: 26848625
                SO-VID: e4ed5f8b-e3f1-4b1d-aea6-7e93a7efaf35
                Copyright © Copyright: © 2016 Chen et al.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 16 July 2015
                Date accepted : 21 January 2016
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: fezf1-as1,fezf1,colorectal cancer,long non-coding rna
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: fezf1-as1, fezf1, colorectal cancer, long non-coding rna

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