LncGata6 maintains stemness of intestinal stem cells and promotes intestinal tumorigenesis

Abstract

The intestinal epithelium harbours remarkable self-renewal capacity that is driven by Lgr5 intestinal stem cells (ISCs) at the crypt base. However, the molecular mechanism controlling Lgr5 ISC stemness is incompletely understood. We show that a Gata6 long noncoding RNA (lncGata6) is highly expressed in ISCs. LncGata6 knockout or conditional knockout in ISCs impairs the stemness of ISCs and epithelial regeneration. Mechanistically, lncGata6 recruits the NURF complex onto the Ehf promoter to induce its transcription, which promotes the expression of Lgr4/5 to enhance Wnt signalling activation. Moreover, the human orthologue lncGATA6 is highly expressed in the cancer stem cells of colorectal cancer and promotes tumour initiation and progression. Antisense oligonucleotides against lncGATA6 exhibit strong therapeutic efficacy on colorectal cancer. Thus, targeting lncGATA6 will have potential clinical applications in colorectal cancer treatment as an ideal therapeutic target.

The Translational Landscape of the Human Heart

“…Microproteins Are Produced from ''Noncoding'' RNAs with Known Functions Aided by improved transcript annotations (e.g., Figure 4E), we identify translated sORFs in 27 human and 5 mouse lncRNAs with previously assigned noncoding functions, including LINC-PINT (also known as lincRNA-Mkln1) (Huarte et al, 2010), JPX (Tian et al, 2010), CRNDE (Graham et al, 2011), NEAT1 (Clemson et al, 2009, DANCR (Kretz et al, 2012), BANCR (Flockhart et al, 2012, and GATA6-AS1 (also known as lncGATA6) (Zhu et al, 2018). Moreover, we detect translated sORFs in the heart function-related lncRNAs myheart (Han et al, 2014), chaer (Wang et al, 2016), UPPERHAND (also known as UPH or HAND2-AS1; Anderson et al, 2016b), ZFAS1 (Zhang (A) Histogram showing the length distribution (in aa) of newly detected short ORFs in translated lncRNAs.…”

Genome-wide mapping of DNA-binding sites identifies stemness-related genes as directly repressed targets of SNAIL1 in colorectal cancer cells

“…Knowledge about the cellular origin of CRCs and the extensive characterization of ISCs concerning essential transcription factors, key regulatory circuits of ISC fate, and distinguishing gene expression signatures [19-23, 56, 57] allowed us to examine at a molecular level how SNAIL1 proteins affect stemness features. The observed repression of multiple genes of crucial importance for ISCs [37,56,58] argues that SNAIL1-induced EMT interferes with stemness aspects of CRC cells. This is consistent with several reports demonstrating that stemness and tumorinitiating capacities are not necessarily linked to mesenchymal cell fates [9,17,18,59].…”

Template-free synthesis of high degree crystallinity zeolite Y with micro–meso–macroporous structure

“…The rst one was based on the application of templates during the process of crystallization, the former being surface-active substances, [9][10][11] polymers, 12,13 starch, 14 carbon nanotubes, 17 coal aerogel, [18][19][20] and nanosized CaCO 3 . 21 The application of templates enabled to form the zeolite mesopores of 0.15 through 0.70 cm 3 g À1 volume and of 100 through 500 m 2 g À1 surface area as well as to control the pore size within the range of 5-40 nm. The drawbacks of the technique were the low accessibility, high cost, and poor crystallinity degree of the materials obtained.…”