Publication: MicroRNA-143-3p targets pyruvate carboxylase expression and controls proliferation and migration of MDA-MB-231 cells
Issued Date
2019-11-30
Resource Type
ISSN
10960384
00039861
00039861
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2-s2.0-85074362953
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Mahidol University
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SCOPUS
Bibliographic Citation
Archives of Biochemistry and Biophysics. Vol.677, (2019)
Suggested Citation
Pannapa Pinweha, Caroline A. Phillips, Philip A. Gregory, Xiaochun Li, Pakawan Chuayboonya, Phanuphol Mongkolsiri, Gregory J. Goodall, Sarawut Jitrapakdee MicroRNA-143-3p targets pyruvate carboxylase expression and controls proliferation and migration of MDA-MB-231 cells. Archives of Biochemistry and Biophysics. Vol.677, (2019). doi:10.1016/j.abb.2019.108169 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/50030
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Title
MicroRNA-143-3p targets pyruvate carboxylase expression and controls proliferation and migration of MDA-MB-231 cells
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Abstract
© 2019 Pyruvate carboxylase (PC) is a biotin-containing enzyme that converts pyruvate to oxaloacetate. We have previously shown that PC is overexpressed in highly invasive cancer cell lines where it supports biosynthesis during rapid cell growth. Here, we show that miR-143-3p suppresses the expression of PC in MDA-MB-231 cells by targeting its conserved binding site in the 3′-untranslated region (UTR) of human PC mRNA. Incorporation of the PC 3′UTR into a luciferase reporter gene inhibited expression of luciferase by 50% while mutation of the miR-143-3p binding site abrogated this inhibitory effect in MDA-MB-231 cells but not in low aggressive MCF-7 cell line. Transfection of miR-143-3p mimic or overexpression of miR-143-3p using tetracycline-inducible system in MDA-MB-231 cells down-regulated expression of both endogenous PC mRNA and protein by 40% and 50% respectively, confirming the regulatory role of miR-143-3p in PC expression. Induction of miR-143-3p expression at low and high levels lowered proliferation, metabolic activity and migration of MDA-MB-231 cells, in a dose-dependent manner. Re-expression of PC in MDA-MB-231 cells which were induced to express miR-143-3p partially restored migration but not proliferation, indicating that miR-143-3p regulates proliferation and migration through multiple pathways.