title: MiR-19b/20a/92a regulates the self-renewal and proliferation of gastric cancer stem cells.
abstract: Human gastric cancers contain a population of gastric cancer stem cells (GCSCs) that can undergo self-renewal and multipotent differentiation. GCSCs can be enriched with EpCAM+/CD44+ gastric cancer cells. However, the underlying mechanisms controlling the balance of GCSC self-renewal and differentiation remain to be explored. Because miRNAs can regulate cancer cell fates, we compared miRNA expression in tumorspheric cancer cells enriched with GCSCs and more differentiated cells. We found that the miR-17-92 cluster members miR-19b, miR-20a and miR-92a were gradually reduced during the differentiation of GCSCs. Therefore, we speculated that miR-17-92 members might regulate the self-renewal ability of GCSCs. By downregulating miR-19b, miR-20a and miR-92a in EpCAM+/CD44+ GCSCs, or overexpressing them in EpCAM-/CD44- non-GCSC populations, we found that miR-19b, miR-20a and miR-92a could sustain the self-renewal function of GCSCs. Furthermore, we found that miR-19b, miR-20a and miR-92a could also promote the proliferation of gastric cancer cells. miR-17-92 targeted the E2F1 and HIPK1 proteins, which suppressed Wnt-β-catenin signaling. A real-time PCR analysis of miR-19b, miR-20a and miR-92a expression in 97 gastric cancer specimens suggested that miR-92a could be used as an independent prognostic factor in gastric cancer. This study showed that several members of the miR-17-92 cluster, miR-19b, miR-20a and miR-92a, might play important roles in the development of gastric cancer stem cells and that miR-92a has the potential to be used as a predictive prognostic marker in gastric cancer.
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Yang
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Sijun
authors.initials: S
authors.lastname: Hu
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Shi
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D035683:MicroRNAs
keywords: Cancer stem cell; Gastric cancer; Self-renewal; Wnt/β-catenin; miR-17-92