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A Novel Long Non-Coding RNA-KAT7 Is Low Expressed in Colorectal Cancer

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A Novel Long Non-Coding RNA-KAT7 Is Low Expressed in Colorectal Cancer Wang et al. Cancer Cell Int (2019) 19:40 https://doi.org/10.1186/s12935-019-0760-y Cancer Cell International PRIMARY RESEARCH Open Access A novel long non-coding RNA-KAT7 is low expressed in colorectal cancer and acts as a tumor suppressor Qingmei Wang1,2†, Rongzhang He1,3†, Tan Tan1,2†, Jia Li1, Zheng Hu1, Weihao Luo1, Lili Duan1, Wenna Luo1 and Dixian Luo1,2* Abstract Background: The abnormal expression of many long non-coding RNAs (lncRNAs) has been reported in the progres- sion of various tumors. However, the potential biological roles and regulatory mechanisms of long non-coding RNAs in the development of colorectal cancer (CRC) have not yet been fully elucidated. Therefore, it is crucial to identify that lncRNAs can be used for the clinical prevention and treatment of CRC. Methods: In our previous work, we identifcated a novel lncRNA, lncRNA-KAT7, and found that the expression of lncRNA-KAT7 in CRC tissues was signifcantly lower than that in matched normal intestinal tissues, and the expression in CRC cell lines was lower than that of normal intestinal epithelial cells (P < 0.05). Besides, the expression of lncRNA- KAT7 is negative associated with age, tumor size, tumor diferentiation, lymph node metastasis of CRC patients. The potential biological efects and molecular mechanisms of lncRNA-KAT7 in CRC were evaluated using a series of CCK-8 assay, clone formation assay, EdU proliferation assay, scratch determination, transwell determination, western blot analysis, and nude subcutaneous tumorigenesis model construction cell and animal experiments. Results: The expression of lncRNA-KAT7 in CRC tissues was lower than that in matched normal tissues and nor- mal intestinal epithelial cells (P < 0.05). Decreased expression of lncRNA-KAT7 is associated with clinicopathological features of poor CRC patients. In vitro experiments showed that up-regulation of lncRNA-KAT7 expression in CRC cells inhibited cell proliferation and migration. In vivo animal experiments showed that the lncRNA-KAT7 also inhibited tumor growth. Western blot analysis showed that the expression of lncRNA-KAT7 was up-regulated in HCT116 cells, the expression of E-cadherin increased, and the expression of Vimentin, MMP-2 and β-catenin protein was down- regulated so did the phosphorylation NF-κB P65. The results confrm that the expression of lncRAN-KAT7 can inhibit the malignant phenotype of CRC cells. Conclusions: Up to now, as a novel lncRNA, lncRNA-KAT7 has not any relevant research and reports. The results confrm that the expression of lncRNA-KAT7 can inhibit the malignant phenotype of CRC cells. And it can be used as a new diagnostic biomarker and therapeutic target for the development of CRC. Keywords: lncRNA-KAT7, Colorectal cancer, Proliferation, Invasion, Migration, Tumor suppressor *Correspondence: [email protected] †Qingmei Wang, Rongzhang He and Tan Tan have contributed equally to this work 1 Translational Medicine Institute, National & Local Joint Engineering Laboratory for High-throughput Molecular Diagnosis Technology, The First People’s Hospital of Chenzhou, University of South China, Chenzhou 423000, People’s Republic of China Full list of author information is available at the end of the article © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/ publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Wang et al. Cancer Cell Int (2019) 19:40 Page 2 of 13 Background regulating the expression of E-cadherin and Vimentin in Colorectal cancer (CRC) is the leading cause of cancer non-small cell lung cancer. Recently, lncRNA has become mortality in all humans, with approximately 65% of 5-year one of the research hotspots, and lncRNA plays a role in survival rate of CRC patients [1]. In recent years, the inci- oncogenes and tumor suppressor genes in various bio- dence of CRC is on the rise, showing a trend of younger logical processes such as epigenetic regulation, transcrip- age. It is still the focus of global health concerns [2]. Te tion and translation regulation, splicing, imprinting, cell specifc pathogenesis for CRC remains unclear. It has been development, metastasis, and apoptosis [17]. One of the reported that many oncogenes and tumor suppressors are most critical steps in the tumor cell metastasis cascade involved in the development of CRC [3]. In the past dec- is to gain invasive capabilities, including disrupting cell– ade, although the popularity of early CRC screening and cell connections, degrading the cell matrix, and activating the continuous advancement of CRC diagnosis and treat- pathways that control the cytoskeleton dynamics. EMT is ment, the mortality rate of CRC has declined [4]. How- a key factor in biological processes. Epithelial cells lose ever, the mortality rate for patients with CRC metastasis their polarity and convert to a mesenchymal phenotype remains high, and metastasis is still one of the key factors that causes the metastasis of cancer cells [17–21]. EMT causing low clinical efcacy, poor survival period, and enhances the invasion of cancer cells, in response to envi- poor prognosis in CRC patients [5]. Terefore, the prev- ronmental triggers, strengthens invasive functions, and alence and poor outcome of CRC prompted us to reveal also conduces to cell growth and survival [22]. In addi- the pathological mechanism of CRC progression and to tion, the literature also confrms that many lncRNAs pro- fnd efective biomarkers for diagnosis and prognosis. mote or inhibit the occurrence and progression of tumors In recent years, a large amount of evidence suggests by modulating the EMT pathway [23]. that long non-coding RNA (lncRNA) has become an To investigate the role of lncRNAs in CRC, we per- indispensable participant in the development of diferent formed lncRNA microarray assays using “Agilent All- human tumors [6]. Most of human genome is transcribed Human Genome Oligonucleotide Microarray (4 × 44 K)” into RNA, but only about 2% of RNA encodes proteins. (Bohai Biotechnology, Shanghai, China) according to the RNAs lacking protein-coding capacity and open reading standard protocol of the expression profling microar- frame (ORF) are referred to as non-coding RNAs (ncR- ray. Tree pairs of CRC normal tissues and tumor tissues NAs) and are divided into small ncRNAs and long ncR- were tested. It was found that lncRNA-KAT7 was signif- NAs (lncRNAs) groups [7, 8]. More and more lncRNAs cantly lower expressed in CRC tumor tissues than that in have been found to participate in diferent physiologi- normal tissues compared with normal intestinal epithe- cal and pathological processes in the body, but the vast lial tissues in diferentially expressed lncRNAs. KAT7 is majority of their functions are still unclear [9]. LncRNAs an lncRNA located on the human chromosome 17, plus are non-coding transcripts of 200 nucleotides or more, the hg19 region, which contains 575 transcripts without and most of which are located in nuclear. Tey have no 5′ cap structure3′ polyadenylation tail (Fig. 1a, b), Kozak ORF that results in the loss of translation capacity and sequence or ORF, and with a PhyloSCF score of 342 emerges as essential regulators of cell growth and tumor (Fig. 1c). Biopredictive software suggests that lncRNA- metastasis [10]. Many lncRNAs are expressed at low lev- KAT7 does not have protein coding capability. LncRNA- els and show tissue and cell type-specifc expression pat- KAT7 was signifcantly decreased in CRC tumor tissues, terns, whereas the abnormal expression of lncRNAs is indicating that lncRNA-KAT7 may be involved in tumo- attributed to the pathogenesis of some malignant tumors rigenesis and progression of CRC. including CRC [11]. It has been reported in the literature To the best of our knowledge, there is no relevant that lncRNA has been identifed as an oncogene, anti- reports on lncRNA-KAT7 in CRC. Terefore, the pur- oncogene and prognostic predictor [12]. pose of this study was to determine the expression and Only a few discovered lncRNAs play a key role in difer- biological efects of lncRNA-KAT7 in CRC in the cellu- ent biological processes [13]. Te abnormal expression of lar, animal level and human specimens, especially its role multiple lncRNAs is associated with CRC, suggesting that in the metastasis of CRC tumors. Tis study provides lncRNA plays an important role in the development of important clues for fnding new CRC biomarkers and CRC. Some lncRNA, such as H19, HOTAIR, MALAT1, preventing and treating targets. CCAT2 expressed highly in CRC, are responsible for cell proliferation, migration, and invasion of CRC [14]. In Materials and methods addition, Ye et al. [15] found that a novel lnc-GNAT1-1 Patients and samples is low-expressed in CRC and acts as a tumor suppressor Tis study included 140 patients with CRC diagnosed by regulating the RKIP-NF-κB-Snail pathway. Miao et al. in the First People’s Hospital of Chenzhou City between [16] found that FOXF1-AS1 afects tumor metastasis by 2014 and 2016. Fresh colorectal neoplasms and matching Wang et al. Cancer Cell Int (2019) 19:40 Page 3 of 13 Wang et al. Cancer Cell Int
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