C19MC drives nucleolar invasion of mitochondria and meiotic nuclear division in human cancers

Goodwin G. Jinesh; Marian T. Smallin; Nino Mtchedlidze; Marco Napoli; John H. Lockhart; Elsa R. Flores; Andrew S. Brohl

iScience (Nov 2024)

C19MC drives nucleolar invasion of mitochondria and meiotic nuclear division in human cancers

Goodwin G. Jinesh,
Marian T. Smallin,
Nino Mtchedlidze,
Marco Napoli,
John H. Lockhart,
Elsa R. Flores,
Andrew S. Brohl

Affiliations

Goodwin G. Jinesh: Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; Corresponding author
Marian T. Smallin: Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
Nino Mtchedlidze: Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
Marco Napoli: Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
John H. Lockhart: Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
Elsa R. Flores: Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; Cancer Biology and Evolution Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
Andrew S. Brohl: Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; Sarcoma Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; Corresponding author

Journal volume & issue: Vol. 27, no. 11
p. 111132

Abstract

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Summary: The chromosome-19 miRNA cluster (C19MC) restricts viruses depending on the multinucleated state of placental trophoblasts. However, the relationship of C19MC to multinucleation is unknown. Here we show that C19MC is coexpressed in multiple cancer type subsets with meiosis-related genes. We discovered a novel meiosis-III that exhibits simultaneous progression of meiotic nuclear division (MND) and cytokinesis. C19MC promotes meiotic bridged-chromosomes to block MND and cytokinesis to generate multinucleated cells. MND starts with the invagination of nuclear membrane to form nucle(ol)ar invasive cytoplasm (NiC), mitochondria and protein cargoes. Aurora-B regulates the efflux of cargos from NiC, whereas C19MC, CDK1, and autophagy promote cargo influx to inflate NiC size for MND progression. Using CRISPR human genetic engineering we demonstrate that the C19MC expression is required for NiC-driven MND and multinucleation. This discovery has impacts on cancer-pathogen interactions, immunotherapy, vertical transmission of viruses, antiviral research and SpCas9-CRISPR therapeutics.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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