miR-32 promotes esophageal squamous cell carcinoma metastasis by targeting CXXC5

MicroRNA-32 (miR-32) functioned as a tumor oncogene in some cancer, which control genes involved in important biological and pathological functions and facilitate the tumor growth and metastasis. However, the role of miR-32 modulates esophageal squamous cell carcinoma (ESCC) malignant transformation has not been clarified. Here, we focused on the function and the underlying molecular mechanism of miR-32 in ESCC. Results discovered a significant increased expression of miR-32 in ESCC tissues and cells. Downregulation of miR-32 inhibited the migration, invasion, adhesion of ESCC cell lines (EC9706 and KYSE450), and the levels of EMT protein in vitro. In vivo, miR-32 inhibitors decrease tumor size, tumor weight, and the number of metastatic nodules. Hematoxylin and eosin (H&E) results revealed that inhibition of miR-32 attenuate lung metastasis. Immunohistochemistry and immunofluorescence assay showed increased level of E-cadherin and decreased level of N-cadherin and Vimentin with treatment of miR-32 inhibitors. Furthermore, miR-32 targeted the 3′-untranslated region (3′-UTR) of CXXC5, and inhibited the level of mRNA and protein of CXXC5. There is a negative correlation between the expressions of CXXC5 and miR-32. Then, after EC9706 and KYSE450 cells cotransfected with si-CXXC5 and miR-32 inhibitors, the ability of cell migration, invasion, and adhesion was significantly reduced. In addition, the protein expression of EMT and TGF-β signaling was also depressed. Collectively, these data supply an insight into the positive role of miR-32 in ESCC progression and metastasis, and its biological effects may attribute the inhibition of TGF-β signaling mediated by CXXC5.     

树突状表皮T细胞在胸腺内发育的研究进展

树突状表皮T淋巴细胞(DETC),特异性分布在表皮组织内,在皮肤免疫监视,皮肤伤面愈合中发挥重要作用.小鼠DETC发育仅涉及胚胎14.5 ～ 18 d这一短暂时间窗,而后则不再产生这类细胞.本综述拟从DETC T细胞受体(TCR)基因重排特点及调控机制,DETC在胸腺中的阳性选择及调控机制等方面进行论述,以期对DETC...     

Autophagy-associated circRNA circATG7 facilitates autophagy and promotes pancreatic cancer progression

Dysregulation of autophagy and circular RNAs (circRNAs) are involved in the pancreatic cancer (PC) progression. However, the regulatory network between circRNAs, autophagy, and PC progression remains unknown. Herein, we demonstrated that autophagy-associated circRNA circ-autophagy related 7 (circATG7) was elevated in PC tissues compared to adjacent tissues, and in PC cells treated with EBSS and hypoxia. circATG7 expression was positively associated with tumor diameter and lymph node invasion in patients with PC. circATG7 overexpression promoted PC cell proliferation, mobility, and autophagy in vitro, while circATG7 knockdown induced the opposite effects. ATG7 inhibition attenuated the effects of circATG7 on the biological functions of PC cells. CircATG7 is located in the cell cytoplasm and nucleus. Cytoplasmic circATG7 sponged miR-766-5p and decreased its expression, and increased the expression of ATG7, a target gene of miR-766-5p. Nuclear circATG7 acted as a scaffold to increase the interaction between the human antigen R protein and ATG7 mRNA and enhanced ATG mRNA stability. Furthermore, we demonstrated that circATG7 regulates PC cell proliferation and metastasis in vivo via ATG7-dependent autophagy. In conclusion, our results demonstrated that circATG7 accelerates PC progression via miR-766-5p/ATG7 and that HUR/ATG7 depends on autophagic flux. Thus, circATG7 may be a potential therapeutic target for PC.Subject terms: Pancreatic cancer, Pancreatic cancer     

Characterizing mobile element insertions in 5675 genomes

Mobile element insertions (MEIs) are a major class of structural variants (SVs) and have been linked to many human genetic disorders, including hemophilia, neurofibromatosis, and various cancers. However, human MEI resources from large-scale genome sequencing are still lacking compared to those for SNPs and SVs. Here, we report a comprehensive map of 36 699 non-reference MEIs constructed from 5675 genomes, comprising 2998 Chinese samples (∼26.2×, NyuWa) and 2677 samples from the 1000 Genomes Project (∼7.4×, 1KGP). We discovered that LINE-1 insertions were highly enriched in centromere regions, implying the role of chromosome context in retroelement insertion. After functional annotation, we estimated that MEIs are responsible for about 9.3% of all protein-truncating events per genome. Finally, we built a companion database named HMEID for public use. This resource represents the latest and largest genomewide study on MEIs and will have broad utility for exploration of human MEI findings.