Pseudohypoxia induced by miR-126 deactivation promotes migration and therapeutic resistance in renal cell carcinoma

Liu, Wei Jun; Wong, Nathan; Haynes, Wesley; Baker, Callie M.; Wang, Xiaowei

doi:10.1016/j.canlet.2017.02.025

Cited by 44 publications

(32 citation statements)

References 46 publications

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“…Serpin Family E Member 1 (SERPINE1) was identified as a miR-126-5p target regulating cell motility. 28 Chronic heart failure was significantly associated with lower circulating levels of miR-126-5p. 29 Lack of miR-126-5p reduced endothelial cell proliferation by derepression of the Notch1 inhibitor delta-like 1 homolog (Dlk1).…”

Section: Discussionmentioning

confidence: 97%

“… 43 Activation of EGFR was demonstrated to accelerate recovery from acute nephrotoxic kidney injury. 44 Because miR-126 has been shown to control endothelial cell homeostasis 30 as well as hypoxia signaling 28 and has also been shown to be an important protective microRNA in AKI, 27 we hypothesize that ciRs-126 may be part of signaling cascade involving LRIG and miR-126, which may have implications as a cytoprotective mechanism in AKI, which is released into the circulation to counteract progressive kidney injury.…”

Section: Discussionmentioning

confidence: 99%

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The Circular RNA ciRs-126 Predicts Survival in Critically Ill Patients With Acute Kidney Injury

Kölling

Seeger

Haddad

et al. 2018

Kidney International Reports

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IntroductionCircular RNAs (circRNAs) have recently been described as novel noncoding regulators of gene expression. They might have an impact on microRNA expression by their sponging activity. The detectability in blood of these RNA transcripts has been demonstrated in patients with cancer and cardiovascular disease. We tested the hypothesis that circulating circRNAs in blood of critically ill patients with acute kidney injury (AKI) at inception of renal replacement therapy may also be dysregulated and associated with patient survival.MethodsWe performed a global circRNA expression analysis using RNA isolated from blood of patients with AKI as well as controls. This global screen revealed several dysregulated circRNAs in patients with AKI. Most highly increased circRNA-array−based transcripts as well as expression of the circRNA target miR-126-5p were confirmed in blood of 109 patients with AKI, 30 age-matched healthy controls, 25 critically ill non-AKI patients, and 20 patients on maintenance hemodialysis by quantitative real-time polymerase chain reaction.ResultsCirculating concentrations of 3 novel circRNAs were amplified in blood of patients with AKI and in controls. Circular RNA sponge of miR-126 (or ciRs-126) was most highly altered compared to healthy controls and disease controls (fold change of 52.1). ciRs-126 was shown to bioinformatically sponge miR-126-5p, which was found to be highly suppressed in AKI patients and hypoxic endothelial cells. Cox regression and Kaplan−Meier curve analysis revealed ciRs-126 as an independent predictor of 28-day survival (P < 0.01).ConclusionCirculating concentrations of circRNAs in patients with AKI are detectable. ciRs-126 may potentially sponge miR-126-5p and acts as a predictor of mortality in this patient cohort.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

The Circular RNA ciRs-126 Predicts Survival in Critically Ill Patients With Acute Kidney Injury

Kölling

Seeger

Haddad

et al. 2018

Kidney International Reports

View full text Add to dashboard Cite

show abstract

“…As an intronic miRNA, miR-126 has been shown to regulate multiple important cell biological processes, such as physiological processes including cell proliferation, apoptosis, differentiation, adhesion, and intercellular interaction 45,46 ; and pathological processes including cell cycle, differentiation, and self-renewal of human acute myeloid leukemia stem cells 47 ; and cell proliferation, survival, apoptosis, migration, invasion, motility, and metastasis of cancer cells 44,46,48 . In the present study, we have shown that miR-126 promotes porcine granulosa cell apoptosis and follicular atresia, demonstrating that miR-126 is required for the functions of granulosa cells in female mammals.…”

Section: Discussionmentioning

confidence: 99%

NORFA, long intergenic noncoding RNA, maintains sow fertility by inhibiting granulosa cell death

Liu

Zhang

et al. 2020

Commun Biol

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Long intergenic non-coding RNAs (lincRNAs) have been proved to be involved in regulating female reproduction. However, to what extent lincRNAs are involved in ovarian functions and fertility is incompletely understood. Here we show that a lincRNA, NORFA is involved in granulosa cell apoptosis, follicular atresia and sow fertility. We found that NORFA was downregulated during follicular atresia, and inhibited granulosa cell apoptosis. NORFA directly interacted with miR-126 and thereby preventing it from binding to TGFBR2 3′-UTR. miR-126 enhanced granulosa cell apoptosis by attenuating NORFA-induced TGF-β signaling pathway. Importantly, a breed-specific 19-bp duplication was detected in NORFA promoter, which proved association with sow fertility through enhancing transcription activity of NORFA by recruiting transcription factor NFIX. In summary, our findings identified a candidate lincRNA for sow prolificacy, and provided insights into the mechanism of follicular atresia and female fertility.

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“…Gong et al reported KLF5 knockdown suppressed hypoxia-induced cisplatin resistance by inhibiting HIF1adependent glycolysis through inactivation of the PI3K/Akt/ mTOR pathway (Gong et al, 2018). Non-coding RNAs can also increase the expression of HIF1a, resulting in platinum resistance Liu et al, 2017b).…”

Section: Hypoxiamentioning

confidence: 99%

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

et al. 2020

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Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit the clinical application of platinum-based treatment. The underlying mechanisms are incredibly complicated. Multiple transporters participate in the active transport of platinum-based antitumor agents, and the altered expression level, localization, or activity may severely decrease the cellular platinum accumulation. Detoxification components, which are commonly increasing in resistant tumor cells, can efficiently bind to platinum agents and prevent the formation of platinum-DNA adducts, but the adducts production is the determinant step for the cytotoxicity of platinum-based antitumor agents. Even if adequate adducts have formed, tumor cells still manage to survive through increased DNA repair processes or elevated apoptosis threshold. In addition, autophagy has a profound influence on platinum resistance. This review summarizes the critical participators of platinum resistance mechanisms mentioned above and highlights the most potential therapeutic targets or predicted markers. With a deeper understanding of the underlying resistance mechanisms, new solutions would be produced to extend the clinical application of platinum-based antitumor agents largely.

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Pseudohypoxia induced by miR-126 deactivation promotes migration and therapeutic resistance in renal cell carcinoma

Cited by 44 publications

References 46 publications

The Circular RNA ciRs-126 Predicts Survival in Critically Ill Patients With Acute Kidney Injury

The Circular RNA ciRs-126 Predicts Survival in Critically Ill Patients With Acute Kidney Injury

NORFA, long intergenic noncoding RNA, maintains sow fertility by inhibiting granulosa cell death

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

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