MicroRNA-140-3p represses the proliferation, migration, invasion and angiogenesis of lung adenocarcinoma cells via targeting TYMS (thymidylate synthetase)

Wan, Shouhong; Liu, Zhimin; Yang, Chen; Mai, Zhitao; Jiang, Mingming; Qin, Di; Sun, Baohua

doi:10.1080/21655979.2021.2009422

Cited by 11 publications

(6 citation statements)

References 47 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The miRNA-140-3p has been considered as an important regulator of NSCLC cells. Wan et al, 2021 reported that miRNA-140-3p represses the proliferation of lung adenocarcinoma cells by targeting thymidylate synthetase [70]; Hu et al, 2022 also reported that miR-140-3p inhibits the progression of NSCLC by targeting Janus kinase 1 [71]. One miRNA may have multiple targets, so it plays a variety of physiological functions [72][73][74].…”

Section: Discussionmentioning

confidence: 99%

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway

Meng

Wang

et al. 2022

J. Cancer

View full text Add to dashboard Cite

Background:The Notch pathway, which is related to the drug-resistance of lung adenocarcinoma (LUAD) type of non-small cell lung cancer (NSCLC) cells, is activated by cleavage of Notch proteins mediated by ADAMs, ADAM10 or ADAM17. Methods: In the present study, our results demonstrated that of these two ADAMs, the expression of ADAM10 in clinical samples of the LUAD type of NSCLC was much higher than that of ADAM17, while miR-140-3p -an miRNA that could target ADAM10 -was identified by an online tool: miRDB (miRNA database). The detail function and mechanism of miR-140-3p in regulating the sensitivity of NSCLC cells to antitumor drugs was systematically explored in vitro and in vivo. Results: In A549, a typical NSCLC LUAD cell line, miR-140-3p decreased ADAM10 expression and repressed activation of the Notch pathway by repressing cleavage of Notch proteins. The expression of miR-140-3p was negatively related to ADAM10 in clinical specimens. Nucleocytoplasmic separation/ subfraction assays showed that miR-140-3p was able to inhibit the cleavage of Notch protein, and led to the accumulation of Notch intracellular domains (NICD) in the nucleus. Overexpression of miR-140-3p enhanced the sensitivity of A549 cells to antitumor agents by targeting the 3'UTR region of ADAM10 mRNA in both cultured cells and in vivo models. Conclusion: ADAM10 plays a major role in LUAD, and miR-140-3p acts on ADAM10 and inhibits its expression and the cleavage of Notch protein, leading to the inhibition the activity of the Notch pathway, and ultimately upregulating LUAD cell sensitivity to anti-tumor drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway

Meng

Wang

et al. 2022

J. Cancer

View full text Add to dashboard Cite

show abstract

“…We first demonstrated that placenta-derived exosomal miR-140-3p and miR-574-3p suppress the proliferation, migration, and tube information of umbilical vein endothelial cells. Despite reports that miR-140 decreases VEGF expression [ 44 , 45 , 46 ], the underlying mechanism remains unclear. Similarly, we observed that miR-140-3p decreased VEGF expression in endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Chemerin-Induced Down-Regulation of Placenta-Derived Exosomal miR-140-3p and miR-574-3p Promotes Umbilical Vein Endothelial Cells Proliferation, Migration, and Tube Formation in Gestational Diabetes Mellitus

Zhang

Shu-qi

et al. 2022

Cells

View full text Add to dashboard Cite

Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes and fetoplacental endothelial dysfunction; however, the underlying mechanisms remain unknown. This study aimed to investigate the effect of placenta-derived exosomal miRNAs on fetoplacental endothelial dysfunction in GDM, as well as to further explore the role of chemerin to this end. Placenta-derived exosomal miR-140-3p and miR-574-3p expression (next-generation sequencing, quantitative real-time PCR), its interactions with cell function (Cell Counting Kit-8, Transwell, tube formation assay), chemerin interactions (Western blotting), and placental inflammation (immunofluorescence staining, enzyme-linked immunosorbent assay) were investigated. Placenta-derived exosomal miR-140-3p and miR-574-3p were downregulated in GDM. Additionally, miR-140-3p and miR-574-3p inhibited the proliferation, migration, and tube formation ability of umbilical vein endothelial cells by targeting vascular endothelial growth factor. Interestingly, miR-140-3p and miR-574-3p expression levels were negatively correlated with chemerin, which induced placental inflammation through the recruitment of macrophage cells and release of IL-18 and IL-1β. These findings indicate that chemerin reduces placenta-derived exosomal miR-140-3p and miR-574-3p levels by inducing placental inflammation, thereby promoting the proliferation, migration, and tube formation of umbilical vein endothelial cells in GDM, providing a novel perspective on the underlying pathogenesis and therapeutic targets for GDM and its offspring complications.

show abstract

“…Reports also indicate several other miRNAs, which in various types of cancer may regulate the level of protein encoded by TYMS and thus affect the sensitivity of cancer cells to 5FU chemotherapy, including miRNA such as miR-140-3p (Wan et al 2021 ), miR-197-3p (Sun et al 2015 ), miR-203a-3p (Li et al 2015a ), miR-218-5p (Li et al 2015b ), miR-330-3p (Xu et al 2017 ), miR-375-3p (Xu et al 2020b ), miR-433-3p (Gotanda et al 2013 ).…”

Section: Mirnas Targeting Tyms Mrnamentioning

confidence: 99%

“…MiR-140-3p has been reported to target the 3’UTR of TYMS mRNA in lung adenocarcinoma cells (Wan et al 2021 ). Interestingly, miR-140-5p levels were also reported to be decreased in CRC specimens taken from patients, but increased in slowly proliferating and chemoresistant CRC CSCs, and furthermore, CRC cells transfected with miR-140 precursor were resistant to 5FU (Song et al 2009 ).…”

Section: Mirnas Targeting Tyms Mrnamentioning

confidence: 99%

MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy

Matuszyk

2022

Mol Med

View full text Add to dashboard Cite

Background The active metabolite of 5-Fluorouracil (5FU), used in the treatment of several types of cancer, acts by inhibiting the thymidylate synthase encoded by the TYMS gene, which catalyzes the rate-limiting step in DNA replication. The major failure of 5FU-based cancer therapy is the development of drug resistance. High levels of TYMS-encoded protein in cancerous tissues are predictive of poor response to 5FU treatment. Expression of TYMS is regulated by various mechanisms, including involving non-coding RNAs, both miRNAs and long non-coding RNAs (lncRNAs). Aim To delineate the miRNAs and lncRNAs network regulating the level of TYMS-encoded protein. Main body Several miRNAs targeting TYMS mRNA have been identified in colon cancers, the levels of which can be regulated to varying degrees by lncRNAs. Due to their regulation by the MALAT1 lncRNA, these miRNAs can be divided into three groups: (1) miR-197-3p, miR-203a-3p, miR-375-3p which are downregulated by MALAT1 as confirmed experimentally and the levels of these miRNAs are actually reduced in colon and gastric cancers; (2) miR-140-3p, miR-330-3p that could potentially interact with MALAT1, but not yet supported by experimental results; (3) miR-192-5p, miR-215-5p whose seed sequences do not recognize complementary response elements within MALAT1. Considering the putative MALAT1-miRNAs interaction network, attention is drawn to the potential positive feedback loop causing increased expression of MALAT1 in colon cancer and hepatocellular carcinoma, where YAP1 acts as a transcriptional co-factor which, by binding to the TCF4 transcription factor/ β-catenin complex, may increase the activation of the MALAT1 gene whereas the MALAT1 lncRNA can inhibit miR-375-3p which in turn targets YAP1 mRNA. Conclusion The network of non-coding RNAs may reduce the sensitivity of cancer cells to 5FU treatment by upregulating the level of thymidylate synthase.

show abstract

MicroRNA-140-3p represses the proliferation, migration, invasion and angiogenesis of lung adenocarcinoma cells via targeting TYMS (thymidylate synthetase)

Cited by 11 publications

References 47 publications

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway

Chemerin-Induced Down-Regulation of Placenta-Derived Exosomal miR-140-3p and miR-574-3p Promotes Umbilical Vein Endothelial Cells Proliferation, Migration, and Tube Formation in Gestational Diabetes Mellitus

MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy

Contact Info

Product

Resources

About