Mechanism and function of decreased FOXO1 in renal cell carcinoma

Zhou, Libin; Yin, Bingde; Liu, Yongchao; Hong, Yan; Zhang, Changcun; Fan, Jia

doi:10.1002/jso.23013

Cited by 28 publications

(22 citation statements)

References 33 publications

(45 reference statements)

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“…Although it has been reported that FoxO1 positively regulates LAL expression in adipocytes, FoxO1 is negatively regulated by Akt and down‐regulated in the majority of human renal tumour samples . Thus, we applied IHC to compare LAL, FoxO1 and phosphorylated Akt (p‐Akt) (Ser473) and total Akt protein levels in adjacent slices of kidney and ccRCC samples.…”

Section: Resultsmentioning

confidence: 99%

“…Although it has been reported that FoxO1 positively regulates LAL expression in adipocytes, 44 FoxO1 is negatively regulated by Akt and down-regulated in the majority of human renal tumour samples. 45,46 Thus, we applied IHC to compare LAL, FoxO1 and phosphorylated Akt (p-Akt) (Ser473) and total Akt protein levels in adjacent slices of kidney and ccRCC samples. Interestingly, the level of p-Akt exhibited a negative correlation with FoxO1 ( Figure 4A) and a strong positive correlation with LAL ( Figure 4A, B) (P < .05).…”

Section: Suppression Of Lal Attenuates Ccrcc Growth and Survival Bymentioning

confidence: 99%

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Lysosomal acid lipase promotes cholesterol ester metabolism and drives clear cell renal cell carcinoma progression

Wang

Tan

et al. 2018

Cell Proliferation

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Section: Resultsmentioning

confidence: 99%

Section: Suppression Of Lal Attenuates Ccrcc Growth and Survival Bymentioning

confidence: 99%

Lysosomal acid lipase promotes cholesterol ester metabolism and drives clear cell renal cell carcinoma progression

Wang

Tan

et al. 2018

Cell Proliferation

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“…A transcriptome analysis of YM155-treated RCC786.0 cells identified up to 200 genes that were differentially expressed in the presence of YM155, the majority of which were associated with the p53 connection pathway and would thus affect survivability, cellular proliferation and cell cycle control. Of these genes, we followed up on four members (tumour suppressors FOXO1 and CYLD ; tumour promoters ID1 and BIRC5 ) that were involved in RCC pathology [5,38,41,45,59,60,61]. BIRC5 encodes survivin expression [48,49,50] and FOXO1 mediates cell cycle arrest and promotes apoptosis [41,42].…”

Section: Discussionmentioning

confidence: 99%

Action of YM155 on clear cell renal cell carcinoma does not depend on survivin expression levels

Sim

Huynh

et al. 2017

PLoS ONE

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The dioxonapthoimidazolium YM155 is a survivin suppressant which has been investigated as an anticancer agent in clinical trials. Here, we investigated its growth inhibitory properties on a panel of immortalized and patient derived renal cell carcinoma (RCC) cell lines which were either deficient in the tumour suppressor von Hippel-Lindau (VHL) protein or possessed a functional copy. Neither the VHL status nor the survivin expression levels of these cell lines influenced their susceptibility to growth inhibition by YM155. Of the various RCC lines, the papillary subtype was more resistant to YM155, suggesting that the therapeutic efficacy of YM155 may be restricted to clear cell subtypes. YM155 was equally potent in cells (RCC786.0) in which survivin expression had been stably silenced or overexpressed, implicating a limited reliance on survivin in the mode of action of YM155. A follow-up in-vitro high throughput RNA microarray identified possible targets of YM155 apart from survivin. Selected genes (ID1, FOXO1, CYLD) that were differentially expressed in YM155-sensitive RCC cells and relevant to RCC pathology were validated with real-time PCR and western immunoblotting analyses. Thus, there is corroboratory evidence that the growth inhibitory activity of YM155 in RCC cell lines is not exclusively mediated by its suppression of survivin. In view of the growing importance of combination therapy in oncology, we showed that a combination of YM155 and sorafenib at ½ x IC50 concentrations was synergistic on RCC786.0 cells. However, when tested intraperitoneally on a murine xenograft model derived from a nephrectomised patient with clear cell RCC, a combination of suboptimal doses of both drugs failed to arrest tumour progression. The absence of synergy in vivo highlighted the need to further optimize the dosing schedules of YM155 and sorafenib, as well as their routes of administration. It also implied that the expression of other oncogenic proteins which YM155 may target is either low or absent in this clear cell RCC.

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“…The rs895819, as an oncomiR, exhibited its oncogenic activity through regulating target genes [60, 61]. It means that down-regulation of miR-27a may contribute to decreased cancer risk through up-regulating the targets.…”

Section: Discussionmentioning

confidence: 99%

Systematic evaluation of cancer risk associated with rs2292832 in miR-149 and rs895819 in miR-27a: a comprehensive and updated meta-analysis

et al. 2016

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The aim of this study is to provide a precise quantification for the association between miR-149 T > C (rs2292832) and miR-27a A > G (rs895819) and the risk of cancer. We conducted a systematic literature review and evaluated the quality of included studies based on Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to assess the strengths of the associations. We identified 40 studies for pooled analyses. Overall, the results demonstrated that the rs2292832 polymorphism was subtly decrease the risk of breast cancer (CT + CC vs TT: OR = 0.83, 95% CI: 0.70–0.98, P = 0.03; CC vs CT + TT: OR = 0.80, 95% CI: 0.68–0.93, P = 0.00), and the rs895819 polymorphism wasassociated with significantly increased cancer risk in the Asian population (AG + GG vs AA: OR = 1.24, 95% CI: 1.03–1.50, P = 0.02) and in colorectal cancer subgroup (GG vs AA: OR = 1.45, 95% CI: 1.10–1.92, P = 0.00; AG + GG vs AA: OR = 1.35, 95% CI: 1.15–1.58, P = 0.00; GG vs AG + AA: OR = 1.36, 95% CI: 1.04–1.77, P = 0.02). In addition, a subtly decreased risk was observed in the Caucasian population and in breast cancer subgroup. In conclusion, the rs2292832 polymorphism was significantly associated with increased breast cancer risk, and the rs895819 polymorphism contributes to the susceptibility of colorectal and breast cancer.

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Mechanism and function of decreased FOXO1 in renal cell carcinoma

Abstract: Reduced expression of FOXO1 is common in RCC and a potentially suitable marker of different histological subtypes and prognosis of cRCC. Increasing expression of FOXO1 by the miR-27a inhibitor could prevent cell growth.

Cited by 28 publications

References 33 publications

Lysosomal acid lipase promotes cholesterol ester metabolism and drives clear cell renal cell carcinoma progression

Lysosomal acid lipase promotes cholesterol ester metabolism and drives clear cell renal cell carcinoma progression

Action of YM155 on clear cell renal cell carcinoma does not depend on survivin expression levels

Systematic evaluation of cancer risk associated with rs2292832 in miR-149 and rs895819 in miR-27a: a comprehensive and updated meta-analysis

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