G6PD activity and gene expression in leukemic cells from G6PD-deficient subjects

Batetta, Barbara; Pulisci, D.; Bonatesta, Rr; Sanna, Francesca; Piras, Simona; Mulas, Michela; Spano, O.; Putzolu, M.; Broccia, G; Dessı̀, Sandra

doi:10.1016/s0304-3835(99)00052-x

Cited by 24 publications

(28 citation statements)

References 18 publications

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“…Functionally, G6PD supplies ribose and NADPH that support biosynthesis and antioxidant defense, and is thus involved in the oxidative stress response [5]. G6PD levels are elevated in various tumors, including melanoma [6], leukemia [7], colon cancers [8], breast cancers [9], and endometrial carcinomas [10]. Our previous data indicated that elevated G6PD levels were also positively correlated with cervical carcinogenesis in 30 to 40-year-old women infected with HR-HPV-16/18.…”

Section: Introductionmentioning

confidence: 99%

miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD

Chang

Xiao

et al. 2016

Oncotarget

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Ectopic glucose-6-phosphate dehydrogenase (G6PD) expression may contribute to tumorigenesis in cervical cancer associated with high-risk human papillomavirus (HR-HPV 16 and 18) infections. Here, we demonstrate that microRNA-1 (miR-1) in association with AGO proteins targets G6PD in HR-HPV-infected human cervical cancer cells. miR-1 inhibited expression of a reporter construct containing a putative G6PD 3′-UTR seed region and suppressed endogenous G6PD expression. Down-regulation of miR-1 increased G6PD expression in cervical cancer cells. Regression analysis revealed that miR-1 levels correlate negatively with the clinicopathologic features in HR-HPV 16/18-infected cervical cancer patients. miR-1 overexpression inhibited proliferation and promoted apoptosis in cervical cancer cells and reduced xenograft tumor growth in nude mice. Conversely, sponge-mediated miR-1 knockdown markedly increased viability and reduced apoptosis in cervical cancer cells and supported neoplasm growth. Restoration of G6PD expression partially reversed the effects of miR-1 overexpression both in vitro and in vivo. In addition, co-transfection of G6PD siRNA and miR-1 sponge partially reversed miR-1 sponge-induced reductions in cell viability and neoplasm growth. These results suggest that miR-1 suppresses the development and progression of HR-HPV 16/18-infected cervical cancer by targeting G6PD and may be a promising novel therapeutic candidate.

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Section: Introductionmentioning

confidence: 99%

miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD

Chang

Xiao

et al. 2016

Oncotarget

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“…In addition, recent studies demonstrated that G6PD was implicated in the development of multiple cancers, including breast cancer, liver cancer, leukaemia etc 25. Leukaemia cells expressed high level of G6PD, even in G6PD-deficient subjects26. In chronic myelomonocytic leukaemia (CMML), overexpression of G6PD mRNA associated with poor diagnosis27.…”

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confidence: 99%

SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation

Wang

et al. 2016

Sci Rep

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Like most other types of cancer cells, leukaemia cells undergo metabolic reprogramming to support rapid proliferation through enhancing biosynthetic processes. Pentose phosphate pathway (PPP) plays a pivotal role in meeting the anabolic demands for cancer cells. However, the molecular mechanism by which PPP contributes to leukaemia remains elusive. Here, we report that leukaemia cell proliferation is dependent on the oxidative branch of PPP, in particular the first and rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD). Knockdown of G6PD reduces NADPH level in acute myeloid leukaemia (AML) cell lines. Exogenous lipid supplements partially restore the proliferation of G6PD-depleted cells. Deacetylase SIRT2 promotes NADPH production through deacetylating G6PD at lysine 403 (K403). Activation of G6PD by SIRT2 supports the proliferation and clonogenic activity of leukaemia cells. Chemical inhibitors against SIRT2 suppress G6PD activity, leading to reduced cell proliferation of leukaemia cells, but not normal hematopoietic stem and progenitor cells. Importantly, SIRT2 is overexpressed in clinical AML samples, while K403 acetylation is downregulated and G6PD catalytic activity is increased comparing to that of normal control. Together, our study reveals that acetylation regulation of G6PD is involved in the metabolic reprogramming of AML, and SIRT2 serves as a promising target for further therapeutic investigations.

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“…Tian and colleagues (1998) found that cancer cells possessed several times higher G6PDH activity. The positive correlation between tumour progression and G6PDH activity was found also for humans (Batetta et al, 1999).…”

Section: Wwwintechopencommentioning

confidence: 60%

Oxidative Stress: Cause and Consequence of Diseases

Gospodaryov¹,

Lushchak²

2012

Oxidative Stress and Diseases

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G6PD activity and gene expression in leukemic cells from G6PD-deficient subjects

Cited by 24 publications

References 18 publications

miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD

miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD

SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation

Oxidative Stress: Cause and Consequence of Diseases

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