Long noncoding RNA OR3A4 promotes metastasis and tumorigenicity in gastric cancer
作者
Guo, XB;Yang, ZG;Zhi, QM;Wang, D;Guo, L;Li, GM;Miao, RZ;Shi, YL;Kuang, YT
作者单位
[Guo, Xiaobo; Yang, Ziguo; Miao, Ruizhen; Shi, Yulong] Shandong Univ, Shandong Prov Hosp, Dept Gastrointestinal Surg, Jinan 250021, Peoples R China.;-;[Zhi, Qiaoming; Kuang, Yuting] Soochow Univ, Affiliated Hosp 1, Dept Gen Surg, Suzhou 215006, Peoples R China.;-;[Wang, Dan] Shandong Univ, Shandong Prov Hosp, Dept Sci, Jinan 250021, Peoples R China.;-;[Wang, Dan] Shandong Univ, Shandong Prov Hosp, Dept Educ, Jinan 250021, Peoples R China.;-;[Li, Guimei] Shandong Univ, Shandong Prov Hosp, Dept Pediat, Jinan 250021, Peoples R China.;-;[Guo, Lei] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Hepatobiliary Surg, Shanghai 200438, Peoples R China.
摘要
The contribution of long noncoding RNAs (lncRNAs) to metastasis of gastric cancer remains largely unknown. We used microarray analysis to identify lncRNAs differentially expressed between normal gastric tissues and gastric cancer tissues and validated these differences in quantitative real-time (qRT)-PCR experiments. The expression levels of lncRNA olfactory receptor, family 3, subfamily A, member 4 (OR3A4) were significantly associated with lymphatic metastasis, the depth of cancer invasion, and distal metastasis in 130 paired gastric cancer tissues. The effects of OR3A4 were assessed by overexpressing and silencing OR3A4 in gastric cancer cells. OR3A4 promoted cancer cell growth, angiogenesis, metastasis, and tumorigenesis in vitro and in vivo. Global microarray analysis combined with RT-PCR, RNA immunoprecipitation, and RNA pull-down analyses after OR3A4 transfection demonstrated that OR3A4 influenced biologic functions in gastric cancer cells via regulating the activation of PDLIM2, MACC1, NTN4, and GNB2L1. Our results reveal OR3A4 as an oncogenic lncRNA that promotes tumor progression, Therefore, lncRNAs might function as key regulatory hubs in gastric cancer progression.
关键词
TAX-MEDIATED TUMORIGENESIS; VEGF-C EXPRESSION; IN-VIVO; VASCULOGENIC MIMICRY; PROSTATE-CANCER; GENE-EXPRESSION; DOWN-REGULATION; CELL-MIGRATION; BREAST-CANCER; CARCINOMA