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Biology subjects

Lemmers, C.

Publications and source records attributed to Lemmers, C..

2 recordsLinked to original sources

CRISPR Activation/Inhibition Experiments Reveal that Expression of Intronic MicroRNA miR-335 Depends on the Promoter Activity of its Host Gene Mest

MicroRNAs are small non-coding RNAs that act as rheostats to modulate gene expression during development, physiology, and disease. Approximately half of mammalian microRNAs are intronic. It is unknown whether intronic miRNA transcription depends on their host gene or a microRNA-specific promoter. Here, we show that CRISPR inhibition of host gene Mest downregulated hosted miR-335 in mouse embryonic stem cells and brain organoids. Reciprocally, CRISPR transactivation of Mest upregulated miR-335. By contrast, activation of miR-335 predicted promoter had no effect. Thus, intronic miR-335 expression depends on the promoter activity of its host gene. This approach could serve to map microRNA promoters.

genomics↗

Loss of cyclin A2 in murine colonic epithelial cells disrupts colon homeostasis by triggering DNA damage and dysplasia and high cyclin A2 expression is a good-prognosis factor in patients with colorectal cancer

To clarify the function of cyclin A2 in colon homeostasis and colorectal cancer (CRC) we generated mice deficient for cyclin A2 in colonic epithelial cells (CEC). Colons of those mice displayed architectural changes in the mucosa, and signs of inflammation as well as an increased proliferation of CEC associated with the appearance of low- and high-grade dysplasia. The main initial events triggering those alterations in cyclin A2 deficient CEC appear to be abnormal mitoses and DNA damage. Cyclin A2 deletion in CEC promoted the development of dysplasia and adenocarcinomas in the murine colitis-associated cancer model. We next explored the status of cyclin A2 expression in clinical CRC samples at the mRNA and protein level and found higher expression in tumors of stage I and II patients compared to those of stage III and IV. A meta-analysis of 11 transcriptome datasets comprising 2,239 primary CRC tumors displayed different CCNA2 (the mRNA coding for cyclin A2) expression levels among the CRC tumor subtypes with highest in CMS1 and lowest in CMS4. Moreover, high expression of CCNA2 was found to be a good prognosis factor independently from other prognostic factors for the CMS1, CMS3 and CMS4 subtypes.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC=\"FIGDIR/small/690404v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (36K):\norg.highwire.dtl.DTLVardef@d9de04org.highwire.dtl.DTLVardef@17f0b4forg.highwire.dtl.DTLVardef@1bf9748org.highwire.dtl.DTLVardef@16520df_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗