The chromatin modifier MORC2 affects glucose metabolism by regulating the expression of lactate dehydrogenase A through a feed forward loop with c-Myc

染色质修饰剂 MORC2 通过与 c-Myc 形成前馈回路来调节乳酸脱氢酶 A 的表达,从而影响葡萄糖代谢

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作者:Rohith Kumar Guddeti, Liz Thomas, Anbarasu Kannan, Prashanthi Karyala, Suresh B Pakala

Abstract

Microrchidia family CW-type zinc finger 2 (MORC2) is a recently identified chromatin modifier with an emerging role in cancer metastasis. However, its role in glucose metabolism, a hallmark of malignancy, remains to be explored. We found that MORC2 is a glucose-inducible gene and a target of c-Myc. Our meta-analysis revealed that MORC2 expression is positively correlated with the expression of enzymes involved in glucose metabolism in breast cancer patients. Furthermore, overexpression of MORC2 in MCF-7 and BT-549 cells augmented the expression and activity of a key glucose metabolism enzyme, lactate dehydrogenase A (LDHA). Conversely, selective knockdown of MORC2 by siRNA markedly decreased LDHA expression and activity and in turn reduced cancer cell migration. Collectively, these findings provide evidence that MORC2, a glucose-inducible gene, modulates the migration of breast cancer cells through the MORC2-c-Myc-LDHA axis.

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