LncRNA CASC15 promotes colon cancer cell proliferation and metastasis by regulating the miR‑4310/LGR5/Wnt/β‑catenin signaling pathway

Previous studies have indicated that overexpression of long noncoding RNA cancer susceptibility 15 (CASC15) may promote tumor development and progression in gastric cancer and hepatocellular carcinoma. However, the function of CASC15 in colon cancer remains unknown. In the present study, the express...

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Veröffentlicht in:Molecular medicine reports 2018-08, Vol.18 (2), p.2269-2276
Hauptverfasser: Jing, Niancai, Huang, Tao, Guo, Huaiyu, Yang, Jili, Li, Mingjing, Chen, Zhuo, Zhang, Yue
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Huang, Tao
Guo, Huaiyu
Yang, Jili
Li, Mingjing
Chen, Zhuo
Zhang, Yue
description Previous studies have indicated that overexpression of long noncoding RNA cancer susceptibility 15 (CASC15) may promote tumor development and progression in gastric cancer and hepatocellular carcinoma. However, the function of CASC15 in colon cancer remains unknown. In the present study, the expression of CASC15 was upregulated in colon cancer tissues and its expression was correlated with clinical Tumor‑Node‑Metastasis stage and tumor metastasis. In addition, knockdown of CASC15 significantly inhibited the proliferation, migration and invasion of colon cancer cells in vitro and in vivo. Following mechanistic experiments, CASC15 was observed to act as a sponge to suppress microRNA (miR)‑4310 that targeted LGR5. Through the inhibition of miR‑4310, CASC15 promoted leucine‑rich repeat‑containing G‑protein coupled receptor 5 (LGR5) expression and consequently activated the Wnt/β‑catenin signaling pathway. The results revealed that the inhibition of the Wnt/β‑catenin signaling pathway in CASC15‑overexpressing colon cancer cells suppressed cellular proliferation, migration and invasion. Collectively, these results demonstrated that CASC15 promoted colon cancer growth and metastasis through the activation of the Wnt/β‑catenin signaling pathway in a miR‑4310/LGR5 dependent manner. Thus, the present study suggested that CASC15 may be a therapeutic target for colon cancer treatment.
doi_str_mv 10.3892/mmr.2018.9191
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However, the function of CASC15 in colon cancer remains unknown. In the present study, the expression of CASC15 was upregulated in colon cancer tissues and its expression was correlated with clinical Tumor‑Node‑Metastasis stage and tumor metastasis. In addition, knockdown of CASC15 significantly inhibited the proliferation, migration and invasion of colon cancer cells in vitro and in vivo. Following mechanistic experiments, CASC15 was observed to act as a sponge to suppress microRNA (miR)‑4310 that targeted LGR5. Through the inhibition of miR‑4310, CASC15 promoted leucine‑rich repeat‑containing G‑protein coupled receptor 5 (LGR5) expression and consequently activated the Wnt/β‑catenin signaling pathway. The results revealed that the inhibition of the Wnt/β‑catenin signaling pathway in CASC15‑overexpressing colon cancer cells suppressed cellular proliferation, migration and invasion. Collectively, these results demonstrated that CASC15 promoted colon cancer growth and metastasis through the activation of the Wnt/β‑catenin signaling pathway in a miR‑4310/LGR5 dependent manner. Thus, the present study suggested that CASC15 may be a therapeutic target for colon cancer treatment.</description><identifier>ISSN: 1791-2997</identifier><identifier>EISSN: 1791-3004</identifier><identifier>DOI: 10.3892/mmr.2018.9191</identifier><identifier>PMID: 29956772</identifier><language>eng</language><publisher>Greece: Spandidos Publications UK Ltd</publisher><subject>Apoptosis ; Cell growth ; Cell migration ; Cell proliferation ; Colon cancer ; Colorectal cancer ; G protein-coupled receptors ; Gastric cancer ; Hepatocellular carcinoma ; Hospitals ; Laboratory animals ; Leucine ; Liver cancer ; Lung cancer ; Medical prognosis ; Metastases ; Metastasis ; MicroRNAs ; miRNA ; Plasmids ; Proteins ; Regulation ; Signal transduction ; Studies ; Therapeutic applications ; Tumorigenesis ; Wnt protein ; β-Catenin</subject><ispartof>Molecular medicine reports, 2018-08, Vol.18 (2), p.2269-2276</ispartof><rights>Copyright Spandidos Publications UK Ltd. 2018</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c290t-9bfd2849cf7d9a66a2768ef56b983d4a0b9a27bec9c1be9736a29205648655b93</citedby><cites>FETCH-LOGICAL-c290t-9bfd2849cf7d9a66a2768ef56b983d4a0b9a27bec9c1be9736a29205648655b93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29956772$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jing, Niancai</creatorcontrib><creatorcontrib>Huang, Tao</creatorcontrib><creatorcontrib>Guo, Huaiyu</creatorcontrib><creatorcontrib>Yang, Jili</creatorcontrib><creatorcontrib>Li, Mingjing</creatorcontrib><creatorcontrib>Chen, Zhuo</creatorcontrib><creatorcontrib>Zhang, Yue</creatorcontrib><title>LncRNA CASC15 promotes colon cancer cell proliferation and metastasis by regulating the miR‑4310/LGR5/Wnt/β‑catenin signaling pathway</title><title>Molecular medicine reports</title><addtitle>Mol Med Rep</addtitle><description>Previous studies have indicated that overexpression of long noncoding RNA cancer susceptibility 15 (CASC15) may promote tumor development and progression in gastric cancer and hepatocellular carcinoma. 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Collectively, these results demonstrated that CASC15 promoted colon cancer growth and metastasis through the activation of the Wnt/β‑catenin signaling pathway in a miR‑4310/LGR5 dependent manner. Thus, the present study suggested that CASC15 may be a therapeutic target for colon cancer treatment.</abstract><cop>Greece</cop><pub>Spandidos Publications UK Ltd</pub><pmid>29956772</pmid><doi>10.3892/mmr.2018.9191</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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source Spandidos Publications Journals; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects Apoptosis
Cell growth
Cell migration
Cell proliferation
Colon cancer
Colorectal cancer
G protein-coupled receptors
Gastric cancer
Hepatocellular carcinoma
Hospitals
Laboratory animals
Leucine
Liver cancer
Lung cancer
Medical prognosis
Metastases
Metastasis
MicroRNAs
miRNA
Plasmids
Proteins
Regulation
Signal transduction
Studies
Therapeutic applications
Tumorigenesis
Wnt protein
β-Catenin
title LncRNA CASC15 promotes colon cancer cell proliferation and metastasis by regulating the miR‑4310/LGR5/Wnt/β‑catenin signaling pathway
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