MicroRNA-146a promotes proliferation, migration, and invasion of HepG2 via regulating FLAP

Zhang, Shubing; Li, Tao; Wang, Lianzi; Lv, Wei; Wang, Shanshan; Ma, Dongyue; Zang, Yan; Zhu, Xinyue; Xu, Yuanhong; Zheng, Lan; Shen, Jilong; Wei, Wei

doi:10.1186/s12935-022-02568-0

Cited by 6 publications

(5 citation statements)

References 47 publications

(58 reference statements)

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“…These genes include DDIT3 (DNA damage-inducible transcript 3) [34], FANCM (Fanconi anemia, complementation group M) [35], Merlin tumor suppressor [36,37], NME1 (NME/NM23 nucleoside diphosphate kinase 1) [38], SMAD4 [39,40]. FLAP (5-Lipoxygenase Activating Protein) [41], HTT (Huntingtin) [42], CADM2 (cell adhesion molecule 2) [43], IRAK1 (interleukin 1 receptor associated kinase 1), TRAF6 (tumor necrosis factor receptor-associated factor-6), and NUMB (NUMB Endocytic Adaptor Protein) [44]. Which of these genes mediate the oncogenic effect of mir146a in bladder cancer warrants further study.…”

Section: Discussionmentioning

confidence: 99%

Impacts of Mir146a Genotypes on Bladder Cancer Risk in Taiwan

Wang,

Chang,

Liao

et al. 2023

Biomedicines

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The aim of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) in mir146a and mir196a and bladder cancer (BLCA) risk in Taiwan. The genotypes of mir146a rs2910164 and mir196a rs11614913 were determined in 375 BLCA patients and 375 healthy controls using PCR-RFLP methodology, and their associations with BLCA risk were evaluated. The study also measured the serum expression level of mir146a using quantitative RT-PCR. The results showed that the distributions of CC, CG and GG genotypes of mir146a rs2910164 were 31.7%, 45.6% and 22.7% in the control group, and 21.9%, 44.3% and 33.8% in the case group, respectively. In logistic regression analyses, the heterozygous variant genotype CG carriers showed a marginally significant association with increased BLCA risk (OR = 1.41, 95% CI = 0.99–2.01), while the homozygous variant genotype GG carriers had a 2.17-fold increased risk of BLCA (OR = 2.17, 95%CI = 1.46–3.21). Moreover, carriers of the GG/CG genotypes had significantly higher serum levels of mir146a than those with the CC genotype (p < 0.0001), indicating a genotype–phenotype correlation. In contrast, mir196a rs11614913 was not associated with BLCA risk. Therefore, the genotypes of mir146a rs2910164 may serve as a useful biomarker for predicting the risk of BLCA.

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Section: Discussionmentioning

confidence: 99%

Impacts of Mir146a Genotypes on Bladder Cancer Risk in Taiwan

Wang,

Chang,

Liao

et al. 2023

Biomedicines

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“…Numerous studies have shown that most miRNAs exert regulatory effects by binding specific target genes [40][41][42] . In addition, miRNAs can be used as new tumor markers, and have applications including early tumor detection, efficacy monitoring and evaluation, and prognostication.…”

Section: Discussionmentioning

confidence: 99%

MiR-378a-3p acts as a tumor suppressor in gastric cancer via directly targeting RAB31 and inhibiting the Hedgehog pathway proteins GLI1/2

Liu

et al. 2022

Cancer Biol Med

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Objective: To improve the prognosis of patients with gastric cancer (GC), more effective therapeutic targets are urgently needed. Increasing evidence indicates that miRNAs are involved in the progression of various tumors, and RAS-associated protein in the brain 31 (RAB31) is upregulated and promotes the progression of multiple malignant tumors. Here, we focused on identifying RAB31-targeted miRNAs and elucidating their potential mechanism in the progression of GC. Methods: RAB31 and miR-378a-3p expression levels were detected in paired fresh GC tissues and GC cell lines. Bioinformatics analysis was used to predict the miRNAs targeting RAB31 and the relationships between RAB31 and other genes. Dual-luciferase reporter assays were applied to verify the targeted interaction relationship. CCK-8, colony formation, flow cytometry, wound healing, and Transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of GC cells. Tumorsphere formation assays were performed to assess the stemness of gastric cancer stem cells. Related proteins were detected by Western blot. Xenograft assays in nude mice were performed to explore the effect of miR-378a-3p in vivo. Results: We report the first evidence that miR-378a-3p is downregulated in GC, whereas its overexpression inhibits proliferation, invasion, and migration as well as promotes apoptosis in GC cells. Mechanistically, miR-378a-3p inhibits the progression of GC by directly targeting RAB31. Restoring RAB31 expression partially offsets the inhibitory effect of miR-378a-3p. Further research revealed that miR-378a-3p inhibits GLI1/2 in the Hedgehog signaling pathway and attenuates the stemness of gastric cancer stem cells. Finally, xenograft assays showed that miR-378a-3p inhibits GC tumorigenesis in vivo. Conclusions: MiR-378a-3p inhibits GC progression by directly targeting RAB31 and inhibiting the Hedgehog signaling pathway proteins GLI1/2.

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“…Cytotoxicity of the compounds was examined with sulforhodamine B (SRB) assay following standard protocol with some modifications as following details. 9 Cells (1 × 10 3 cells/well) 10 , 11 were seeded into a 96-well plate and incubated overnight. Then, the media were replaced with media containing various concentrations of the specified compounds and incubated further for 72 hours while 0.3% dimethyl sulfoxide (DMSO) was used as a vehicle control.…”

Section: Methodsmentioning

confidence: 99%

Anti-proliferative Effects of Pinocembrin Isolated From Anomianthus dulcis on Hepatocellular Carcinoma Cells

Saengboonmee,

Thithuan,

Mahalapbutr

et al. 2024

Integr Cancer Ther

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Background: Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer. Anomianthus dulcis (Dunal) J.Sinclair (syn. Uvaria dulcis) has been used in Thai traditional medicine in various therapeutic indications. Phytochemical constituents of A. dulcis have been isolated and identified. However, their effects on liver cancer and the associated mechanisms have not been elucidated. Methods: Dry flowers of A. dulcis were extracted using organic solvents, and chromatographic methods were used to purify the secondary metabolites. The chemical structures of the pure compounds were elucidated by analysis of spectroscopic data. Cytotoxicity against HCC cells was examined using SRB assay, and the effects on cell proliferation were determined using flow cytometry. The mechanisms underlying HCC inhibition were examined by molecular docking and verified by Western blot analysis. Results: Among 3 purified flavonoids, pinocembrin, pinostrobin, and chrysin, and 1 indole alkaloid (3-farnesylindole), only pinocembrin showed inhibitory effects on the proliferation of 2 HCC cell lines, HepG2 and Li-7, whereas chrysin showed specific toxicity to HepG2. Pinocembrin was then selected for further study. Flow cytometric analyses revealed that pinocembrin arrested the HCC cell cycle at the G1 phase with a minimal effect on cell death induction. Pinocembrin exerted the suppression of STAT3, as shown by the molecular docking on STAT3 with a better binding affinity than stattic, a known STAT3 inhibitor. Pinocembrin also suppressed STAT3 phosphorylation at both Tyr705 and Ser727. Cell cycle regulatory proteins under the modulation of STAT3, namely cyclin D1, cyclin E, CDK4, and CDK6, are substantially suppressed in their expression levels. Conclusion: Pinocembrin extracted from A. dulcis exerted a significant growth inhibition on HCC cells via suppressing STAT3 signaling pathways and its downstream-regulated genes.

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MicroRNA-146a promotes proliferation, migration, and invasion of HepG2 via regulating FLAP

Cited by 6 publications

References 47 publications

Impacts of Mir146a Genotypes on Bladder Cancer Risk in Taiwan

Impacts of Mir146a Genotypes on Bladder Cancer Risk in Taiwan

MiR-378a-3p acts as a tumor suppressor in gastric cancer via directly targeting RAB31 and inhibiting the Hedgehog pathway proteins GLI1/2

Anti-proliferative Effects of Pinocembrin Isolated From Anomianthus dulcis on Hepatocellular Carcinoma Cells

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