Biology subjects

Sugawara, A.

Publications and source records attributed to Sugawara, A..

3 recordsLinked to original sources

bioRxiv2026

Thiol methyltransferase METTL7B coordinates lipid metabolism and promotes tumor progression in pancreatic cancer

Dysregulated lipid metabolism drives cancer progression, yet the molecular mechanisms linking lipid accumulation to pancreatic cancer remain poorly understood. Here, we identify methyltransferase-like 7B (METTL7B) as a key regulator of lipid metabolism and tumor progression in pancreatic cancer. Integrated analysis of large-scale transcriptomic datasets revealed that METTL7B is upregulated in pancreatic cancer compared with normal tissues, and elevated METTL7B expression is associated with poor patient prognosis. Functional experiments demonstrated that METTL7B is required for pancreatic cancer cell proliferation, migration, and metastasis. We identified hepatocyte nuclear factor 4 (HNF4A) and hepatocyte nuclear factor 4{gamma} (HNF4G), well-established regulators of lipid homeostasis, as transcription factors that directly upregulate METTL7B expression in pancreatic cancer cells. Moreover, we showed that METTL7B localizes around lipid droplets and promotes their accumulation in pancreatic cancer cells. Lipidomic analyses revealed that METTL7B depletion selectively reduces long-chain triacylglycerols and increases shorter-chain ceramides, while also modulating other lipid droplet-related lipid classes in a chain-length-dependent manner. Collectively, these findings suggest that METTL7B regulates lipid metabolism and malignant behavior in pancreatic cancer and may represent a potential therapeutic target.

molecular biology↗

bioRxiv2024

Interparental Gene Conversion in General Population: A Novel Mechanism For Loss of Heterozygosity

Gene conversion is a process in which genetic material from a donor sequence is unidirectionally copied to an acceptor sequence during the homologous recombination repair of a DNA double-strand break. Although gene conversion has been widely studied in the context of meiosis, hereditary diseases, and cancer development, gene conversion between parental homologs in the zygotes remains controversial. Here, we developed a method to detect interparental gene conversions by focusing on Mendelian errors and identified gene conversion events in one out of every 21.8 births. Some of these events were observed in genetic regions, potentially affecting offspring phenotypes. Interparental gene conversion leads to the offspring inheriting two identical alleles from one parent, resulting in a loss of heterozygosity. Our findings suggest that naturally occurring interparental gene conversions may provide a novel mechanism for the development of certain genetic diseases.

genomics↗

bioRxiv2021

Astroglial CD38 regulates social memory and synapse formation through SPARCL1 in the medial prefrontal cortex

Social behavior is essential for the health, survival and reproduction of animals, yet the role of astrocytes in social behavior is largely unknown. CD38 is critical for social behaviors by regulating oxytocin release from hypothalamic neurons. On the other hand, CD38 is most abundantly expressed in astrocytes especially in the postnatal cortex, and is important for astroglial development. Here, we demonstrate that astroglial CD38 plays a pivotal role in the social behavior. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, specifically impaired social memory without any other behavioral abnormalities. Morphological analysis revealed reductions in spine numbers, mature spines and excitatory synapse numbers in the pyramidal neurons of the medial prefrontal cortex (mPFC) due to deletion of astroglial CD38 in the postnatal brain. Astrocyte-conditioned medium (ACM) of CD38 KO astrocytes reduced synaptogenesis of cortical neurons by reducing extracellular SPARCL1, a synaptogenic protein. Finally, the release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. Our data indicate that astroglial CD38 developmentally regulates social memory and neural circuit formation in the developing brain by promoting synaptogenesis through SPARCL1.

neuroscience↗