PIKE-A Modulates Mitochondrial Metabolism through Increasing SDHA Expression Mediated by STAT3/FTO Axis

Previous studies have shown that phosphoinositide 3-kinase enhancer-activating Akt (PIKE-A) is involved in the regulation of several biological processes in cancer. In our previous study, we demonstrated a crucial function of PIKE-A in cancer energy metabolism by regulating pentose phosphate pathway...

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Published inInternational journal of molecular sciences Vol. 23; no. 19; p. 11304
Main Authors Sun, Mingming, Yan, Qi, Qiao, Yaya, Zhao, Huifang, Wang, Yingzhi, Shan, Changliang, Zhang, Shuai
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.10.2022
MDPI
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Summary:Previous studies have shown that phosphoinositide 3-kinase enhancer-activating Akt (PIKE-A) is involved in the regulation of several biological processes in cancer. In our previous study, we demonstrated a crucial function of PIKE-A in cancer energy metabolism by regulating pentose phosphate pathway (PPP) flux. However, whether PIKE-A regulates energy metabolism through affecting mitochondrial changes are poorly understood. In the present study, we show that PIKE-A promotes mitochondrial membrane potential, leading to increasing proliferation of glioblastoma cell. Mechanistically, PIKE-A affects the expression of respiratory chain complex Ⅱ succinate dehydrogenase A (SDHA), mediated by regulating the axis of STAT3/FTO. Taken together, these results revealed that inhibition of PIKE-A reduced STAT3/FTO/SDHA expression, leading to the suppression of mitochondrial function. Thus, our findings suggest the PIKE-A/STAT3/FTO/SDHA axis as promising anti-cancer treatment targets.
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content type line 23
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms231911304