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Modified Blood Collection from Tail Veins of Non-anesthetized Mice with a Vacuum Blood Collection System and Eyeglass Magnifier

Blood sample collection is the basis of experimental animal research. It is of importance to obtain adequate blood samples for various research purposes. ...

Huazhong University of Science and Technology

Recent studies suggest the emerging roles of armadillo (ARM) family proteins in tumor progression. However, the functions and underlying mechanisms of ARM members in tumorigenesis and aggressiveness of neuroblastoma (NB) remain to be determined. Herein, we identify armadillo repeat containing 12 (ARMC12) as an ARM member associated with NB progression. ARMC12 promotes the growth and aggressiveness of NB cell lines. Mechanistically, ARMC12 physically interacts with retinoblastoma binding protein 4 (RBBP4) to facilitate the formation and activity of polycomb repressive complex 2, resulting in transcriptional repression of tumor suppressive genes. Blocking the interaction between ARMC12 and RBBP4 by cell-penetrating inhibitory peptide activates the downstream gene expression and suppresses the tumorigenesis and aggressiveness of NB cells. Both ARMC12 and RBBP4 are upregulated in NB tissues, and are associated with unfavorable outcome of patients. These findings suggest the crucial roles of ARMC12 in tumor progression and a potential therapeutic approach for NB.

Armadillo repeat containing 12 promotes neuroblastoma progression through interaction with retinoblastoma binding protein 4.

Argonaute 2 (AGO2), the core component of microRNA (miRNA)-induced silencing complex, plays a compelling role in tumorigenesis and aggressiveness. However, the mechanisms regulating the functions of AGO2 in cancer still remain elusive. Herein, we indentify one intronic circular RNA (circRNA) generated from AGO2 gene (circAGO2) as a novel regulator of AGO2-miRNA complexes and cancer progression. CircAGO2 is up-regulated in gastric cancer, colon cancer, prostate cancer, and neuroblastoma, and is associated with poor prognosis of patients. CircAGO2 promotes the growth, invasion, and metastasis of cancer cells in vitro and in vivo. Mechanistic studies reveal that circAGO2 physically interacts with human antigen R (HuR) protein to facilitate its activation and enrichment on the 3'-untranslated region of target genes, resulting in reduction of AGO2 binding and repression of AGO2/miRNA-mediated gene silencing associated with cancer progression. Pre-clinically, administration of lentivirus-mediated short hairpin RNA targeting circAGO2 inhibits the expression of downstream target genes, and suppresses the tumorigenesis and aggressiveness of xenografts in nude mice. In addition, blocking the interaction between circAGO2 and HuR by cell-penetrating inhibitory peptide represses the tumorigenesis and aggressiveness of cancer cells. Taken together, these results indicate that oncogenic circAGO2 drives cancer progression through facilitating HuR-repressed functions of AGO2-miRNA complexes.

Circular RNA circAGO2 drives cancer progression through facilitating HuR-repressed functions of AGO2-miRNA complexes.

Circular RNAs (circRNA), a subclass of noncoding RNA characterized by covalently closed continuous loops, play emerging roles in tumorigenesis and aggressiveness. However, the functions and underlying mechanisms of circRNA in regulating Wnt/β-catenin signaling and cancer progression remain elusive. Here we screen cis-acting circRNA generated by β-catenin (CTNNB1)/transcription factor 7 like 2 genes and identify one intronic circRNA derived from CTNNB1 (circ-CTNNB1) as a novel driver of cancer progression. Circ-CTNNB1 was predominantly expressed in the nucleus, upregulated in cancer tissues and cell lines, and associated with unfavorable outcome in cancer patients. Circ-CTNNB1 promoted β-catenin activation, growth, invasion, and metastasis in cancer cells. Circ-CTNNB1 bound DEAD-box polypeptide 3 (DDX3) to facilitate its physical interaction with transcription factor Yin Yang 1 (YY1), resulting in transactivation of YY1 and transcriptional alteration of downstream genes associated with β-catenin activation and cancer progression. Pre-clinically, administration of lentivirus-mediated short hairpin RNA targeting circ-CTNNB1 or a cell-penetrating inhibitory peptide blocking the circ-CTNNB1-DDX3 interaction inhibited downstream gene expression, tumorigenesis, and aggressiveness in cancer cells. Taken together, these results demonstrate cis-acting circ-CTNNB1 as a mediator of β-catenin signaling and cancer progression through DDX3-mediated transactivation of YY1.

Article	Year
Armadillo repeat containing 12 promotes neuroblastoma progression through interaction with retinoblastoma binding protein 4. Nature communications\| PubMed ID: 30026490	2018
Circular RNA circAGO2 drives cancer progression through facilitating HuR-repressed functions of AGO2-miRNA complexes. Cell death and differentiation\| PubMed ID: 30341421	2018
Cis-acting circ-CTNNB1 promotes β-catenin signaling and cancer progression via DDX3-mediated transactivation of YY1. Cancer research\| PubMed ID: 30563889	2018

Huanhuan Li

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