Modulation of microRNA processing by 5‐lipoxygenase

Uebbing, Stella; Kreiß, Marius; Scholl, Friederike; Häfner, Ann-Kathrin; Sürün, Duran; Garscha, Ulrike; Werz, Oliver; Basavarajappa, Devaraj; Samuelsson, Bengt; Rådmark, Olof; Suess, Beatrix; Steinhilber, Dieter

doi:10.1096/fj.202002108r

Cited by 12 publications

(10 citation statements)

References 52 publications

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“…Gene encoding miRNAs is transcribed by RNA polymerase (Pol) II/III and processed via an evolutionarily conserved pathway [ 48 ] ( Figure 1(a) ). Specifically, a long primary transcript (pri-miRNA) shapes a characteristic hairpin structure that can be cleaved into a precursor miRNA (pre-miRNA) of approximately 60 nt in length by the microprocessor complex consisting of Drosha and DiGeorge syndrome critical region 8 (DGCR8) [ 49 ]. The produced pre-miRNA is then translocated to the cytoplasm via exportin 5 and Ran-GTP complex.…”

Section: Roles Of Main Noncoding Rnas In Cancermentioning

confidence: 99%

The Targeting of Noncoding RNAs by Quercetin in Cancer Prevention and Therapy

Wang

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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The dietary flavonoid quercetin is ubiquitously distributed in fruits, vegetables, and medicinal herbs. Quercetin has been a focal point in recent years due to its versatile health-promoting benefits and high pharmacological values. It has well documented that quercetin exerts anticancer actions by inhibiting cell proliferation, inducing apoptosis, and retarding the invasion and metastasis of cancer cells. However, the exact mechanism of quercetin-mediated cancer chemoprevention is still not fully understood. With the advances in high-throughput sequencing technologies, the intricate oncogenic signaling networks have been gradually characterized. Increasing evidence on the close association between noncoding RNA (ncRNAs) and cancer etiopathogenesis emphasizes the potential of ncRNAs as promising molecular targets for cancer treatment. Available experimental studies indicate that quercetin can dominate multiple cancer-associated ncRNAs, hence repressing carcinogenesis and cancer development. Thus, modulation of ncRNAs serves as a key mechanism responsible for the anticancer effects of quercetin. In this review, we focus on the chemopreventive effects of quercetin on cancer pathogenesis by targeting cancer-relevant ncRNAs, supporting the viewpoint that quercetin holds promise as a drug candidate for cancer chemoprevention and chemotherapy. An in-depth comprehension of the interplay between quercetin and ncRNAs in the inhibition of cancer development and progression will raise the possibility of developing this bioactive compound as an anticancer agent that could be highly efficacious and safe in clinical practice.

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Section: Roles Of Main Noncoding Rnas In Cancermentioning

confidence: 99%

The Targeting of Noncoding RNAs by Quercetin in Cancer Prevention and Therapy

Wang

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Biosynthesis of microRNAs is now described in detail and involves a series of sequential processes, including the formation of primary miRNA transcripts (pri-miRNAs) by RNA polymerase II, their subsequent cleavage in the nucleus by Drosha endonuclease to form pre-miRNAs. After transport into the cytoplasm, they are subsequently processed by a multiprotein complex, including Dicer [ 133 , 134 ].…”

Section: Role Of Micrornasmentioning

confidence: 99%

“…Interestingly, 5-LOX can modulate miRNA processing in monocytic cells. It has been shown that 5-LOX can interact with human Dicer [ 133 , 145 , 146 ]. Dicer, which is involved in microRNA biogenesis, is known to interact with cellular proteins through its N-terminal domain.…”

Section: Role Of Micrornasmentioning

confidence: 99%

Genetic and Epigenetic Regulation of Lipoxygenase Pathways and Reverse Cholesterol Transport in Atherogenesis

Kotlyarov

2022

Genes

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Atherosclerosis is one of the most important medical and social problems of modern society. Atherosclerosis causes a large number of hospitalizations, disability, and mortality. A considerable amount of evidence suggests that inflammation is one of the key links in the pathogenesis of atherosclerosis. Inflammation in the vascular wall has extensive cross-linkages with lipid metabolism, and lipid mediators act as a central link in the regulation of inflammation in the vascular wall. Data on the role of genetics and epigenetic factors in the development of atherosclerosis are of great interest. A growing body of evidence is strengthening the understanding of the significance of gene polymorphism, as well as gene expression dysregulation involved in cross-links between lipid metabolism and the innate immune system. A better understanding of the genetic basis and molecular mechanisms of disease pathogenesis is an important step towards solving the problems of its early diagnosis and treatment.

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“…Canonically, primary miRNAs (pri-miRNAs) are transcribed, which are further cleaved by Microprocessor comprised of RNase III enzyme DROSHA and DGCR8 to yield the pre-miRNAs. The pre-miRNAs are exported to cytoplasm where they were cleaved by DICER to generate mature miRNAs ( Spadotto et al, 2020 ; Uebbing et al, 2021 ). miR-214 is located in the DNM3OS transcript unit which gives rise to mature miR-214 ( Qin et al, 2012 ; Savary et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

SPINT1-AS1 Drives Cervical Cancer Progression via Repressing miR-214 Biogenesis

Song

Liu

Liang

et al. 2021

Front. Cell Dev. Biol.

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Accumulating evidences have revealed the dysregulated expressions and critical roles of non-coding RNAs in various malignancies, including cervical cancer. Nevertheless, our knowledge about the vast majority of non-coding RNAs is still lacking. Here we identified long non-coding RNA (lncRNA) SPINT1-AS1 as a novel cervical cancer-associated lncRNA. SPINT1-AS1 was increased in cervical cancer and correlated with advanced stage and poor prognosis. SPINT1-AS1 was a direct downstream target of miR-214, a well-known tumor suppressive microRNA (miRNA) in cervical cancer. Intriguingly, SPINT1-AS1 was also found to repress miR-214 biogenesis via binding DNM3OS, the primary transcript of miR-214. The interaction between SPINT1-AS1 and DNM3OS repressed the binding of DROSHA and DGCR8 to DNM3OS, blocked DNM3OS cleavage, and therefore repressed mature miR-214 biogenesis. The expression of SPINT1-AS1 was significantly negatively correlated with miR-214 in cervical cancer tissues, supporting the reciprocal repression between SPINT1-AS1 and miR-214 in vivo. Through downregulating mature miR-214 level, SPINT1-AS1 upregulated the expression of β-catenin, a target of miR-214. Thus, SPINT1-AS1 further activated Wnt/β-catenin signaling in cervical cancer. Functionally, SPINT1-AS1 drove cervical cancer cellular proliferation, migration, and invasion in vitro, and also tumorigenesis in vivo. Deletion of the region mediating the interaction between SPINT1-AS1 and DNM3OS, overexpression of miR-214, and inhibition of Wnt/β-catenin signaling all reversed the roles of SPINT1-AS1 in cervical cancer. Collectively, these findings identified SPINT1-AS1 as a novel cervical cancer-associated oncogenic lncRNA which represses miR-214 biogenesis and activates Wnt/β-catenin signaling, highlighting its potential as prognostic biomarker and therapeutic target for cervical cancer.

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Modulation of microRNA processing by 5‐lipoxygenase

Cited by 12 publications

References 52 publications

The Targeting of Noncoding RNAs by Quercetin in Cancer Prevention and Therapy

The Targeting of Noncoding RNAs by Quercetin in Cancer Prevention and Therapy

Genetic and Epigenetic Regulation of Lipoxygenase Pathways and Reverse Cholesterol Transport in Atherogenesis

SPINT1-AS1 Drives Cervical Cancer Progression via Repressing miR-214 Biogenesis

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