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      Functional role of long non-coding RNA CASC19/miR-140-5p/CEMIP axis in colorectal cancer progression in vitro

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          Abstract

          BACKGROUND

          Long non-coding RNAs (lncRNAs) are widely involved in tumor regulation. Nevertheless, the role of the lncRNA cancer susceptibility 19 (CASC19) in colorectal cancer (CRC) has yet to be fully clarified.

          AIM

          To explore the effect of CASC19 on proliferation and metastasizing ability of CRC cells.

          METHODS

          CASC19 expression in human CRC tissues, pair-matched adjacent normal colon tissues, and CRC cells was detected using quantitative real-time PCR (qRT-PCR). CASC19 expression, as well as its relation to overall survival, was extrapolated by Kaplan-Meier survival analysis together with multivariable Cox regression assay. In vitro experiments were performed to confirm whether CASC19 regulates CRC cell invasion, migration, proliferation, and apoptosis.

          RESULTS

          CASC19 expression was markedly upregulated in CRC tissues and CRC cell lines ( P < 0.05). qRT-PCR revealed that CASC19 expression was higher in 25 tissue samples from patients with aggressive CRC compared with the 27 tissue samples from patients with nonaggressive CRC ( P < 0.05). Higher CASC19 expression was associated with poorer patient prognoses. Furthermore, in vitro experiments demonstrated that CASC19 overexpression enhanced CRC cell invasion, migration, and proliferation. CASC19 overexpression enhanced the expression of cell migration inducing hyaluronidase 1 (CEMIP) and epithelial-mesenchymal transition markers. MiR-140-5p was found to be able to bind directly to CASC19 and CEMIP. Overexpression of miR-140-5p reversed the effect of CASC19 on cell proliferation and tumor migration, as well as suppressed CASC19-induced CEMIP expression.

          CONCLUSION

          CASC19 positively regulates CEMIP expression through targeting miR-140-5p. CASC19 may possess an oncogenic function in CRC progression, highlighting its potential as an essential biomarker in CRC diagnosis and therapy.

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          Most cited references49

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          Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry.

          Most cancer cells predominantly produce energy by glycolysis rather than oxidative phosphorylation via the tricarboxylic acid (TCA) cycle, even in the presence of an adequate oxygen supply (Warburg effect). However, little has been reported regarding the direct measurements of global metabolites in clinical tumor tissues. Here, we applied capillary electrophoresis time-of-flight mass spectrometry, which enables comprehensive and quantitative analysis of charged metabolites, to simultaneously measure their levels in tumor and grossly normal tissues obtained from 16 colon and 12 stomach cancer patients. Quantification of 94 metabolites in colon and 95 metabolites in stomach involved in glycolysis, the pentose phosphate pathway, the TCA and urea cycles, and amino acid and nucleotide metabolisms resulted in the identification of several cancer-specific metabolic traits. Extremely low glucose and high lactate and glycolytic intermediate concentrations were found in both colon and stomach tumor tissues, which indicated enhanced glycolysis and thus confirmed the Warburg effect. Significant accumulation of all amino acids except glutamine in the tumors implied autophagic degradation of proteins and active glutamine breakdown for energy production, i.e., glutaminolysis. In addition, significant organ-specific differences were found in the levels of TCA cycle intermediates, which reflected the dependency of each tissue on aerobic respiration according to oxygen availability. The results uncovered unexpectedly poor nutritional conditions in the actual tumor microenvironment and showed that capillary electrophoresis coupled to mass spectrometry-based metabolomics, which is capable of quantifying the levels of energy metabolites in tissues, could be a powerful tool for the development of novel anticancer agents that target cancer-specific metabolism.
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            HOTAIR: an oncogenic long non-coding RNA in different cancers

            Long non-coding RNAs (lncRNAs) refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression. Different lncRNAs exist throughout the genome. LncRNAs are also known for their roles in different human diseases such as cancer. HOTAIR is an lncRNA that plays a role as an oncogenic molecule in different cancer cells, such as breast, gastric, colorectal, and cervical cancer cells. Therefore, HOTAIR expression level is a potential biomarker for diagnostic and therapeutic purposes in several cancers. This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 (PRC2). In this review, we describe the molecular function and regulation of HOTAIR and its role in different types of cancers.
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              LncRNA SNHG7 sponges miR-216b to promote proliferation and liver metastasis of colorectal cancer through upregulating GALNT1

              Accumulating evidence suggests long noncoding RNAs (lncRNAs) play an important role in cancer progression. However, the function of lncRNA SNHG7 in colorectal cancer (CRC) remains unclear. In this study, SNHG7 expression was significantly upregulated in CRC tissues, especially in aggressive cases. In accordance, high level of SNHG7 was observed in CRC cell lines compared to normal colon cells. Furthermore, SNHG7 overexpression promoted the proliferation, migration, and invasion of CRC cell lines, while SNHG7 depletion inhibited invasion and cell viability in vitro. Mechanistically, knockdown of SNHG7 inhibited GALNT1 and EMT markers (E-cadherin and Vimentin). Importantly, SNHG7 directly interacted with miR-216b and downregulation of miR-216b reversed efficiently the suppression of GALNT1 induced by SNHG7 siRNA. Moreover, overexpression of SNHG7 significantly enhanced the tumorigenesis and liver metastasis of SW480 cells in vivo. SNHG7 positively regulated GALNT1 level through sponging miR-216b, and played an oncogenic role in CRC progression. Together, our study elucidated the role of SNHG7 as an miRNA sponge in CRC, and shed new light on lncRNA-directed diagnostics and therapeutics in CRC.
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                Author and article information

                Contributors
                Journal
                World J Gastroenterol
                World J. Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                14 April 2019
                14 April 2019
                : 25
                : 14
                : 1697-1714
                Affiliations
                Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China
                Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China
                Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China
                Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China
                Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China. qf@ 123456medmail.com.cn
                Author notes

                Author contributions: Qi F designed and coordinated the research; Wang XD performed the majority of experiments, analyzed the data, and wrote the paper; Lu J, Lin YS, and Gao C contributed new reagents or analytic tools.

                Supported by the National Natural Science Foundation of China, No. 81570375.

                Corresponding author: Feng Qi, FRCS (Gen Surg), MD, PhD, Academic Research, Chief Doctor, Director, Doctor, Full Professor, Professor, Research Scientist, Senior Researcher, Senior Scientist, Surgeon, Surgical Oncologist, Teacher, Department of General Surgery, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, China. qf@ 123456medmail.com.cn

                Telephone: +86-13752115987 Fax: +86-22-60363901

                Article
                jWJG.v25.i14.pg1697
                10.3748/wjg.v25.i14.1697
                6465939
                31011255
                8348364c-5a77-41b3-9e27-492109729a71
                ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 13 January 2019
                : 6 March 2019
                : 15 March 2019
                Categories
                Basic Study

                colorectal cancer,long non-coding rna,microrna,proliferation,metastasis

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