title: c-Myc-induced, long, noncoding H19 affects cell proliferation and predicts a poor prognosis in patients with gastric cancer.
abstract: Gastric cancer (GC) is one of the most frequent cancers worldwide. Recent studies have shown that long noncoding RNAs (lncRNAs) play critical roles in multiple biological processes, including oncogenesis. The present study aimed to evaluate the potential role of lncRNA H19 in GC. qRT-PCR was performed to investigate the expression of H19 in tumor tissues and corresponding non-tumor lung tissues from 80 patients with GC and in GC cell lines. The Kaplan-Meier method and Cox proportional hazards analysis were used to evaluate the association between H19 expression and overall survival time (OS). The biological significance of H19 was evaluated using siRNAs in vitro. We also constructed a c-Myc plasmid to investigate the cause of the altered expression of H19 in the progression of GC. The results show that lncRNA H19 is overexpressed in tumor tissues compared with adjacent normal tissues. An advanced tumor-node-metastasis stage was positively correlated with increased H19 expression (P < 0.001), and a high H19 expression was associated with poor OS and can be regarded as an independent predictor of the OS of GC patients (P = 0.042). MTT and colony formation assays confirmed that H19 expression affects GC cell proliferation in vitro. Furthermore, exogenous c-Myc significantly induces H19 expression, and the expression of H19 was positively correlated with the c-Myc levels in the 80 samples used in our study (Pearson correlation coefficient = -0.687). In conclusion, our study demonstrates that the altered expression of lncRNA H19, which is induced by c-Myc, is involved in the development and progression of GC by regulating cell proliferation and shows that H19 may be a potential diagnostic and prognostic target in patients with GC.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Er-Bao
authors.initials: EB
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Han
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Yin
authors.forename: Rong
authors.initials: R
authors.lastname: Kong
authors.forename: Wei
authors.initials: W
authors.lastname: De
authors.forename: Jinfei
authors.initials: J
authors.lastname: Chen
mesh_terms: D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: C094335:H19 long non-coding RNA; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; D012333:RNA, Messenger