PRDM1 silences stem cell-related genes and inhibits proliferation of human colon tumor organoids

Proceedings of the National Academy of Sciences of the United States of America
Changlong LiuPhillip J Buckhaults

Abstract

PRDM1 is a tumor suppressor that plays an important role in B and T cell lymphomas. Our previous studies demonstrated that PRDM1β is a p53-response gene in human colorectal cancer cells. However, the function of PRDM1β in colorectal cancer cells and colon tumor organoids is not clear. Here we show that PRDM1β is a p53-response gene in human colon organoids and that low PRDM1 expression predicts poor survival in colon cancer patients. We engineered PRDM1 knockouts and overexpression clones in RKO cells and characterized the PRDM1-dependent transcript landscapes, revealing that both the α and β transcript isoforms repress MYC-response genes and stem cell-related genes. Finally, we show that forced expression of PRDM1 in human colon cancer organoids prevents the formation and growth of colon tumor organoids in vitro. These results suggest that p53 may exert tumor-suppressive effects in part through a PRDM1-dependent silencing of stem cell genes, depleting the size of the normal intestinal stem cell compartment in response to DNA damage.

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Citations

Jun 21, 2020·Molecular Carcinogenesis·Ritsuko IwanagaKristin Bruk Artinger
Mar 7, 2020·Immunology and Cell Biology·Miles B HortonPhilip D Hodgkin
Apr 16, 2020·International Journal of Molecular Sciences·Amelia CasamassimiCiro Abbondanza
Nov 27, 2019·World Journal of Stem Cells·Maria Teresa ValentiDonato Zipeto
Sep 2, 2020·Diseases of the Colon and Rectum·Reece K DeHaanEmina H Huang
Jan 2, 2021·Frontiers in Pharmacology·Lujun ShenWeijun Fan
May 12, 2021·Communications Biology·Juil Kim, Yuseok Moon

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