Hui Yang

Purpose Pannexin-1 (PANX1) channel participates in the development and progression of many tumor types, however, its role of PANX1 in invasive pituitary adenoma (PA) remains unknown. The current study was designed to investigate the role of PANX1 in invasion of PA. Methods We examined the expression of PANX1 in 116 surgical invasion and non-invasion PA samples (60 for bulk transcriptome and 56 for immunohistochemistry). The effects of PANX1 on PA growth were assessed in vitro and xenograft models. Meanwhile, the metabolism changes of PA cells are explored via transcriptomics and metabolomics using integration strategy. Results PANX1 is significantly upregulated in invasive PA compared with noninvasive PA and pituitary gland, and have a potential diagnostic signature for invasive PA. Accordingly, overexpression of PANX1 could promote the proliferation and invasion of GH3 and MMQ cell lines in vitro and in vivo. Further metabolomics results confirme that overexpression of PANX1 could trigger changes in several metabolic pathways of GH3 cells. Among the dysregulated cellular metabolites, decreased intracellular ATP suggeste that PANX1 may promote the invasion of PA through impacting extracellular ATP concentration. Mechanistically, extracellular ATP might promote Ca²⁺ influx and upregulated the expression of MMP2/9 by activating P2X7R. Additionally, PANX1-ATP-P2 X7R signaling pathway might enhance GH3 cell invasion by remodeling the actin cytoskeleton. Conclusion Our findings point to a pivotal role of PANX1 in promoting PA invasion, which indicated a potential therapeutic target for invasive PA.

Prokaryotes are equipped with a variety of resistance strategies to survive frequent viral attacks or invading mobile genetic elements. Among these, CRISPR–Cas surveillance systems are abundant and have been studied extensively. This Review focuses on CRISPR–Cas type VI Cas13 systems that use single-subunit RNA-guided Cas endonucleases for targeting and subsequent degradation of foreign RNA, thereby providing adaptive immunity. Notably, distinct from single-subunit DNA-cleaving Cas9 and Cas12 systems, Cas13 exhibits target RNA-activated substrate RNase activity. This Review outlines structural, biochemical and cell biological studies toward elucidation of the unique structural and mechanistic principles underlying surveillance effector complex formation, precursor CRISPR RNA (pre-crRNA) processing, self-discrimination and RNA degradation in Cas13 systems as well as insights into suppression by bacteriophage-encoded anti-CRISPR proteins and regulation by endogenous accessory proteins. Owing to its programmable ability for RNA recognition and cleavage, Cas13 provides powerful RNA targeting, editing, detection and imaging platforms with emerging biotechnological and therapeutic applications.

Prokaryotic clustered regularly interspaced short palindromic repeats and CRISPR associated (CRISPR‐Cas) systems provide adaptive immunity by using RNA‐guided endonucleases to recognize and eliminate invading foreign nucleic acids. Type II Cas9, type V Cas12, type VI Cas13, and type III Csm/Cmr complexes have been well characterized and developed as programmable platforms for selectively targeting and manipulating RNA molecules of interest in prokaryotic and eukaryotic cells. These Cas effectors exhibit remarkable diversity of ribonucleoprotein (RNP) composition, target recognition and cleavage mechanisms, and self discrimination mechanisms, which are leveraged for various RNA targeting applications. Here, we summarize the current understanding of mechanistic and functional characteristics of these Cas effectors, give an overview on RNA detection and manipulation toolbox established so far including knockdown, editing, imaging, modification, and mapping RNA‐protein interactions, and discuss the future directions for CRISPR‐based RNA targeting tools.This article is categorized under: RNA Methods > RNA Analyses in Cells RNA Processing > RNA Editing and Modification RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications

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