PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways

Naidu, Srivatsava; Shi, Lei; Magee, Peter; Middleton, Justin; Laganà, Alessandro; Sahoo, Sudhakar; Leong, Hui Sun; Galvin, Melanie; Frese, Kristopher K.; Dive, Caroline; Guzzardo, Vincenza; Fassan, Matteo; Garofalo, Michela

doi:10.1038/s41598-017-14843-6

Cited by 53 publications

(35 citation statements)

References 48 publications

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“…Through bioinformatics analysis, we recognized that TET2 is the target gene of miR‐125a‐5p. Thus far, the role of miR‐125a‐5p in the cardiovascular system (Gareri et al, ; Tiedt et al, ), tumor (Naidu et al, ), apoptosis (Tong et al, ), and inflammation (Banerjee et al, ) has been reported. Moreover, the expression of miR‐125a‐5p is increased in hyperlipidemic (Simionescu, Niculescu, Sanda, Margina, & Sima, ).…”

Section: Introductionmentioning

confidence: 99%

OxLDL induces vascular endothelial cell pyroptosis through miR‐125a‐5p/TET2 pathway

Zeng

Chen

et al. 2018

Journal Cellular Physiology

114

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Pyroptosis participates in the formation and development of atherosclerosis (As) by promoting inflammatory factor release and is closely related to the stability of atherosclerotic plaque. MicroRNAs can regulate the expression of target genes at the posttranscriptional level. Previous studies have shown that miR-125a-5p increases in hyperlipidemic-hyperglycemic conditions and is involved in apoptosis, but its specific role in pyroptosis and As remains unclear. We propose that miR-125a-5p may be implicated in oxidized low-density lipoprotein (oxLDL)-induced vascular endothelial cells (VECs) pyroptosis and therefore conducted the current study. We observed that miR-125a-5p can inhibit tet methylcytosine dioxygenase 2 (TET2) expression at the posttranscription level, resulting in abnormal DNA methylation, mitochondrial dysfunction, and increased reactive oxygen species production, activated nuclear factor-κB that induces activation of inflammasome and maturation, release of proinflammatory cytokines interleukin (IL)-1β and IL-18, and pyroptosis. Given the role of VECs in vascular physiology, oxLDL-induced VEC pyroptosis may promote the development of As. Our current study reveals a novel pathway associated with pyroptosis program regulation, which comprises miR-125a-5p and TET2 in VECs.Modulation of their expression levels may serve as a potential target for therapeutic strategies of As. K E Y W O R D Satherosclerosis, miR-125a-5p, pyroptosis, ROS, TET2

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Section: Introductionmentioning

confidence: 99%

OxLDL induces vascular endothelial cell pyroptosis through miR‐125a‐5p/TET2 pathway

Zeng

Chen

et al. 2018

Journal Cellular Physiology

114

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“…Feng et al demonstrated that PVT1 modulated inflammatory response and cardiac function in a sepsis model through regulating the NF-κB signaling pathway [37]. Naidu et al discovered that miR-23b mediated the regulation in lung tumorigenesis via targeting the NF-κB signaling pathway [38]. This study was limited in vitro Fig.…”

Section: Discussionmentioning

confidence: 95%

Knockdown of lncRNA PVT1 alleviates high glucose-induced proliferation and fibrosis in human mesangial cells by miR-23b-3p/WT1 axis

Zhong

Jiaoe

Xue

et al. 2020

Diabetol Metab Syndr

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Background: Diabetic nephropathy (DN) is a severe complication of diabetes with type 1 and 2. Long non-coding RNAs (lncRNAs) are being found to be involved in the DN pathogenesis. In this study, we aimed to further explore the effect and underlying mechanism of plasmacytoma variant translocation 1 (PVT1) in DN pathogenesis. Methods: The expression levels of PVT1, miR-23b-3p, and Wilms tumor protein 1 (WT1) mRNA were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was performed to determine protein expression. Cell proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetr-azolium (MTS) assay. The targeted correlation between miR-23b-3p and PVT1 or WT1 was verified by dual-luciferase reporter assay. Results: PVT1 and WT1 were highly expressed in the serum of DN patients and high glucose (HG)-induced mesangial cells (MCs). The knockdown of PVT1 or WT1 ameliorated HG-induced proliferation and fibrosis in MCs. Mechanistically, PVT1 modulated WT1 expression through acting as a molecular sponge of miR-23b-3p. The miR-23b-3p/WT1 axis mediated the protective effect of PVT1 knockdown on HG-induced proliferation and fibrosis in MCs. The NF-κB pathway was involved in the regulatory network of the PVT1/miR-23b-3p/WT1 axis in HG-induced MCs. Conclusion: Our study suggested that PVT1 knockdown ameliorated HG-induced proliferation and fibrosis in MCs at least partially by regulating the miR-23b-3p/WT1/NF-κB pathway. Targeting PVT1 might be a potential therapeutic strategy for DN treatment.

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“…Multitudinous cancer‐related miRNAs have been functionally identified so far. MiR‐125a, located in chromosome 19q, has been reported to be in connection with varied cancers, such as ovarian cancer, 30 gliomas, 31 and NSCLC 16,17 . miRNAs participate in the development of a tumor and the progression via modulating concrete targets or pathways 14,32 .…”

Section: Discussionmentioning

confidence: 99%

“…Especially, mounting evidence illustrates that miRNA‐125a (miR‐125a) is in connection with the occurrence, development intersecting with poor prognosis in NSCLC 16,17 . It is common that miRNAs interact with cancer‐relevant genes to participate in the process of tumors 18 .…”

Section: Introductionmentioning

confidence: 99%

miR‐125a regulates HAS1 and inhibits the proliferation, invasion and metastasis by targeting STAT3 in non–small cell lung cancer cells

Huang

Yao

et al. 2020

J of Cellular Biochemistry

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MicroRNA-125a (miR-125a) is related to the occurrence, development, and prognosis of various cancers according to relevant reports. However, its function role and mechanism in non-small cell lung cancer (NSCLC) is yet to be explored. Herein, we investigated the role and preliminary mechanism of miR-125a in NSCLC. First, miR-125a was noticeably downregulated in NSCLC tissues in contrast to adjacent normal tissues through the real-time quantitative polymerase chain reaction (RT-qPCR) assay. The inverted result was observed on the STAT3 and HAS1 expressions.Moreover, miR-125a was expressed at highest level in A549 among four human NSCLC cell lines. Second, functional studies indicated miR-125a restrained proliferation, invasion, migration, metastasis, and advocated apoptosis of NSCLC cells, but had no obvious effect on cell cycle. Next, results indicated that a target of miR-125a was STAT3 on the basis of prediction and confirmation by the dualluciferase reporter assay. RT-qPCR and Western blot assays displayed that miR-125a overexpression conspicuously constrained STAT3 expression at messenger RNA and protein levels. Finally, the binding between HAS1 promoter region and STAT3 was predicted by PROMO database analysis and verified by chromatin immunoprecipitation assay, suggesting that STAT3 was bound with the HAS1 promoter regions.STAT3 overexpression exerted positive effects on HAS1 expression at protein and mRNA levels. Additionally, HAS1-related functional studies illustrated HAS1 pronouncedly suppressed the proliferative, invasive, and migratory potential of NSCLC cells in vitro. Collectively, our findings demonstrated that miR-125a prohibited the proliferation, invasion, and migration of NSCLC cells by HAS1 expression reduction as a result of inhibiting STAT3 expression in NSCLC. This study indicated that miR-125a might be of potential or value for NSCLC treatment. K E Y W O R D SHAS1, metastasis, miR-125a, non-small cell lung cancer, STAT3 -125a regulates HAS1 and inhibits the proliferation, invasion and metastasis by targeting STAT3 in non-small cell lung cancer cells.

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PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways

Cited by 53 publications

References 48 publications

OxLDL induces vascular endothelial cell pyroptosis through miR‐125a‐5p/TET2 pathway

OxLDL induces vascular endothelial cell pyroptosis through miR‐125a‐5p/TET2 pathway

Knockdown of lncRNA PVT1 alleviates high glucose-induced proliferation and fibrosis in human mesangial cells by miR-23b-3p/WT1 axis

miR‐125a regulates HAS1 and inhibits the proliferation, invasion and metastasis by targeting STAT3 in non–small cell lung cancer cells

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