Silencing transcription factor FOXM1 represses proliferation, migration, and invasion while inducing apoptosis of liver cancer stem cells by regulating the expression of ALDH2.

This study is performed to explore the role of transcription factor FOXM1 in promoting the self-renewal and proliferation of liver cancer stem cells (LCSCs) by regulating the expression of acetaldehyde dehydrogenase-2 (ALDH2). CD133+ CD24+ LCSCs were sorted and identified. A series of experiments were carried out to determine the proliferation, colony formation rate, migration, invasion, and apoptosis of LCSCs after interfering with FOXM1. Proliferation-, epithelial-mesenchymal transition (EMT)-, apoptosis-, and stemness-related factors were then detected by western blot analysis. Tumor xenograft in nude mice was used to figure out the role of FOXM1 in tumorigenesis in vivo by regulating ALDH2 expression. Luciferase activity assay was conducted to determine whether FOXM1 could target ALDH2 promoter region and thereby affecting ALDH2 expression. The sorted CD133+ CD24+ Huh-7 cells had the characteristic of stem cells. FOXM1 was highly expressed in CD133+ CD24+ Huh-7 cells. Silencing FOXM1 inhibited the proliferation and colony formation of LCSCs and decreased the expression of proliferating cell nuclear antigen and Ki-67 protein; inhibited the migration, invasion, and EMT of LCSCs while promoting the apoptosis of LCSCs, as well as promoted the expression of Bax and cleaved-caspase-3, and inhibited the expression of Bcl-2. Silencing FOXM1 inhibited the expression of Nanog, Oct4, and Sox2 in LCSCs by decreasing the expression of ALDH2. in vivo experiment, silencing FOXM1 suppressed tumorigenesis of LCSCs by decreasing the expression of ALDH2. Our study provides evidence that silencing FOXM1 inhibits stemness of LCSCs by decreasing the expression of ALDH2, and represses the proliferation, migration, invasion, and tumorigenesis while inducing the apoptosis of LCSCs.

Chen L ，Wu M ，Ji C ，Yuan M ，Liu C ，Yin Q ... -  《-》

8-bromo-7-methoxychrysin inhibits properties of liver cancer stem cells via downregulation of β-catenin.

Quan MF ，Xiao LH ，Liu ZH ，Guo H ，Ren KQ ，Liu F ，Cao JG ，Deng XY ... -  《-》

Isovitexin reduces carcinogenicity and stemness in hepatic carcinoma stem-like cells by modulating MnSOD and FoxM1.

Cao X ，Liu L ，Yuan Q ，Li X ，Cui Y ，Ren K ，Zou C ，Chen A ，Xu C ，Qiu Y ，Quan M ，Zhang J ，Cao J ，Chen X ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

ELK3 promotes the migration and invasion of liver cancer stem cells by targeting HIF-1α.

Lee JH ，Hur W ，Hong SW ，Kim JH ，Kim SM ，Lee EB ，Yoon SK ... -  《-》

Long noncoding RNA LINC00324 exerts protumorigenic effects on liver cancer stem cells by upregulating fas ligand via PU box binding protein.

Hepatocellular carcinoma (HCC) represents a major cause of cancer death, but the molecular mechanism for its development has not yet been well characterized. Long noncoding RNAs (lncRNAs) are involved in a wide range of biological processes via their roles as oncogenes or tumor suppressor genes. The present study aimed to elucidate the role of LINC00324 in HCC through its interaction with Fas ligand (FasL). Initially, microarray-based gene expression profiling of HCC was employed to identify differentially expressed genes. Next, the expression of LINC00324 in HCC tissues and liver cancer stem cell (LCSC) lines was examined using RT-qPCR. Then, the interaction among LINC00324, PU box binding protein (PU.1) and FasL was identified with RIP, ChIP and dual-luciferase reporter gene assays. The effect of LINC00324 on viability, proliferation, migration, invasion, and apoptosis as well as the tumorigenesis of transfected cells was examined with gain- and loss-of-function experiments. LINC00324 and FasL were highly expressed in HCC. LINC00324 regulated FasL expression via interaction with PU.1. Silencing of LINC00324 or FasL suppressed expression of stemness-related genes, cell viability, proliferation, migration, invasion, self-renewal, and tumorigenesis, but enhanced cell apoptosis. Taken together, LINC00324 promotes the expression of FasL through the recruitment of PU.1, which ultimately maintains the biological properties of LCSCs, thus, highlighting LINC00324 as a promising therapeutic candidate for HCC.

Gao J ，Dai C ，Yu X ，Yin XB ，Zhou F ... -  《-》