Chapman, S. N. | Search bioRxiv

bioRxiv2024

Menopause has not evolved as a general trait in mammals: A response to "Do mammals have menopause?"

Reproductive senescence is widespread across mammals, but only a small number of species have physiological reproductive cessation and an extended post-reproductive lifespan. A recent commentary in Cell by Winkler & Goncalves (2023) suggests that menopause is actually a widespread trait of mammals, which would change our understanding of senescence and have implications for the study of menopause in humans. Here, we identify three main issues with the methodology of this commentary: the use of captive populations, the use of maximal lifespan, and misinterpretations of the data sources. We show that this methodology does not support the conclusions at the species-level, and conclude that, in line with the predictions of classic life-history theory, menopause is indeed a rare trait.

evolutionary biology↗

bioRxiv2024

miR-100 and miR-125b Contribute to Enhanced Growth and Invasiveness

Extracellular communication via the transfer of vesicles and nanoparticles is now recognized to play an important role in tumor microenvironment interactions. Cancer cells upregulate and secrete abundant levels of miR-100 and miR-125b that can alter gene expression by both cell- and non-cell-autonomous mechanisms. We previously showed that these miRNAs activate Wnt signaling in colorectal cancer (CRC) through noncanonical pairing with 5 negative regulators of Wnt signaling. To identify additional targets of miR-100 and miR-125b, we used bioinformatic approaches comparing multiple CRC cell lines, including knockout lines lacking one or both of these miRNAs. From an initial list of 96 potential mRNA targets, we tested 15 targets with 8 showing significant downregulation in the presence of miR-100 and miR-125b. Among these, Cingulin (CGN) and Protein tyrosine phosphatase receptor type-R (PTPRR) are downregulated in multiple cancers, consistent with regulation by increased levels of miR-100 and miR-125b. We also show that increased cellular levels of miR-100 and miR-125b enhance 3D growth and invasiveness in CRC and glioblastoma cell lines. Lastly, we demonstrate that extracellular transfer of miR-100 and miR-125b can silence both reporter and endogenous mRNA targets in recipient cells and also increase the invasiveness of recipient spheroid colonies when grown under 3D conditions in type I collagen.

cancer biology↗