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Whether Gas5 acts as an oncogene or anti\u2010oncogene in hepatocellular carcinoma (HCC) remains unclear. In the present study, the expression and role of Gas5 in HCC were investigated in vitro and in vivo. Lower expression levels of Gas5 were determined in HCC tissues and cells by quantitative reverse transcription\u2010polymerase chain reaction. Overexpressed Gas 5 lentiviral vectors were constructed to analyze their influence on cell viability, migration, invasion, and apoptosis. Fluorescence in situ hybridization was used to identify the subcellular localization of Gas5. Protein complexes that bound to Gas5 were isolated from HepG2 cells through pull\u2010down experiments and analyzed by mass spectrometry. A series of novel Gas5\u2010interacting proteins were identified and bioinformatics analysis was carried out. These included ribosomal proteins, proteins involved in protein folding, sorting, and transportation in the ER, some nucleases and protein enzymes involved in gene transcription, translation, and other proteins with various functions.78\u2009kDa glucose\u2010regulated protein (GRP78) was identified as a direct target of Gas5 by Rip\u2010qPCR and Western blot analysis\u00a0assay. Gas5 inhibited HepG2 cell growth and induced cell apoptosis via upregulating CHOP to activate the ER stress signaling pathway. Further studies indicated that the knockdown of CHOP by shRNA partially reversed Gas5\u2010mediated apoptosis in HepG2 cells. Magnetic resonance imaging\u00a0showed that the ectopic expression of Gas5 inhibited the growth of HCC in nude mice. These findings suggest that Gas5 functions as a tumor suppressor and induces apoptosis through activation of ER stress by targeting the CHOP signal pathway in HCC.<\/jats:p>","DOI":"10.1002\/jcb.30159","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T14:56:35Z","timestamp":1634309795000},"page":"231-247","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Long noncoding RNA Gas5 induces cell apoptosis and inhibits tumor growth via activating the CHOP\u2010dependent endoplasmic reticulum stress pathway in human hepatoblastoma HepG2 cells"],"prefix":"10.1002","volume":"123","author":[{"given":"Wei\u2010Yi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Second Affiliated Hospital Shantou University Medical College Shantou Guangdong Province 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