The inhibition of miR-126 in cell migration and invasion of cervical cancer through regulating ZEB1

Xu, Jiqin; Wang, Hongyun; Wang, Huiyan; Chen, Qing; Zhang, Li; Song, Chao; Zhou, Qianqian; Hong, Ying

doi:10.1186/s41065-019-0087-7

Cited by 34 publications

(24 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The situation would be much clearer if we could show a direct link between miR-126-3p target genes and suppression of the PI3K/PDK1/Akt pathway as alternative pathways and target proteins associated with miR-126-3p are possible. In fact, Xu et al reported that miR-126-3p inhibited cell proliferation and migration via the target protein ZEB1, which is associated with mesenchymal-related protein (49). We did not conduct knockdown or inhibitor experiments of endogenous miR-126-3p, downstream of the PI3K/AKT pathway or a xenograft model to demonstrate the potential application of miR-126-3p into human patients.…”

Section: Discussionmentioning

confidence: 92%

MicroRNA‑126‑3p suppresses HeLa cell proliferation, migration and invasion, and increases apoptosis via the PI3K/PDK1/AKT pathway

et al. 2020

View full text Add to dashboard Cite

We previously reported that relative to normal cervical mucus, microRNA 126-3p (miR-126-3p) is present in significantly greater amounts in the cervical mucus of patients with overt cervical cancer or precursor lesions. Here, we investigated the effects of enforced miR-126-3p expression in the cervical cancer cell line, HeLa, on proliferation, migration, invasion, apoptosis and protein expression. We transfected HeLa cells with miR-126-3p miRNA and found that proliferation, migration and invasion by cell counting, wound healing, cell migration and invasion assay were significantly reduced in these cells relative to those transfected with a negative control mimic. The levels of phosphoinositide 3 kinase (PI3K), phosphorylated 3-phosphoinositide-dependent protein kinase-1 (p-PDK1) and p-AKT proteins were lower in the miR-126-3p-transfected cells. Phosphorylated 70S6K (p-p70S6K), phosphorylated glycogen synthase kinase 3β (p-GSK3β), phosphorylated S6K (p-S6K), cyclin D1, phosphorylated p21-activated kinase 1 (p-PAK1), Rho associated coiled-coil containing protein kinase 1 (ROCK1), myotonic dystrophy-related CDC42-binding kinases α (MRCKα) and phospholipase C γ1 (p-PLCγ1) were also downregulated. This suggests that downstream effectors of the PI3K/PDK1/AKT pathway are targets for inhibition by miR-126-3p. In contrast, apoptotic-related proteins including the BCL-2-associated agonist of cell death (Bad), B-cell lymphoma-extra-large (Bcl-xL) and BCL-2-associated X (Bax), were all upregulated by miR-126-3p, resulting in increased caspase 3/7 activity and apoptosis. Thus, enforced expression of miR-126-3p inhibited cell migration and invasion and also induced apoptosis by regulating the PI3K/PDK1/AKT pathway in HeLa cells. Hence, high levels of miR-126-3p may inhibit cervical carcinogenesis, and targeting the PI3K/PDK1/AKT pathway via miR-126-3p could represent a new approach for treating patients with cervical cancer.

show abstract

Section: Discussionmentioning

confidence: 92%

MicroRNA‑126‑3p suppresses HeLa cell proliferation, migration and invasion, and increases apoptosis via the PI3K/PDK1/AKT pathway

et al. 2020

View full text Add to dashboard Cite

show abstract

“…[13][14][15] However, ZEB1 is reported abnormally up-regulated in cases with CC, which affects the proliferation, metastatic behavior, and EMT of CC cells. 16,17 In the present study, we inferred that miR-139-5p-ZEB1 was a molecular regulator of the growth, invasion, and EMT of CC, and thus we conducted relevant studies to verify it.…”

Section: Introductionmentioning

confidence: 71%

<p><em>MiR-139-5p-ZEB1</em> is a Molecular Regulator of Growth, Invasion, and Epithelial-to-Mesenchymal Transition of Cervical Cancer</p>

Sun

Wang

Liu

et al. 2020

CMAR

View full text Add to dashboard Cite

“…Only two genes (Supplementary Tables 1 and 2) showed large and significant fold change in the opposite direction between IPF and control. The upregulated in IPF is PRSS3, a well-known oncogene that promote cell migration and cancer metastasis [32], while the down-regulated in IPF is MIR126, which functions as a tumor suppressor that inhibit cell migration [33]. Thus, changes in both genes support enhanced cell migration in IPF, in contrast to the prediction made by GOplot.…”

Section: Discussionmentioning

confidence: 91%

Klotho antagonizes pulmonary fibrosis through suppressing pulmonary fibroblasts activation, migration, and extracellular matrix production: a therapeutic implication for idiopathic pulmonary fibrosis

Huang

Chen

Shen

et al. 2020

Aging

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) has been widely accepted as an aging-related fatal lung disease with a therapeutic impasse, largely a consequence of the complex and polygenic gene architecture underlying the molecular pathology of IPF. Here, by conducting an integrative network analysis on the largest IPF case-control RNA-seq dataset to date, we attributed the systems-level alteration in IPF to disruptions in a handful of biological processes including cell migration, transforming growth factor-β (TGF-β) signaling and extracellular matrix (ECM), and identified klotho (KL), a typical anti-aging molecule, as a potential master regulator of those disease-relevant processes. Following experiments showed reduced Kl in isolated pulmonary fibroblasts from bleomycin-exposed mice, and demonstrated that recombinant KL effectively mitigated pulmonary fibrosis in an ex vivo model and alleviated TGF-β-induced pulmonary fibroblasts activation, migration, and ECM production in vitro, which was partially ascribed to FOXF1 and CAV1, two highly co-expressed genes of KL in the IPF. Overall, KL appears to be a vital regulator during pulmonary fibrosis. Given that administration of exogenous KL is a feasible treatment strategy, our work highlighted a promising target gene that could be easily manipulated, leaving the field well placed to further explore the therapeutic potential of KL for IPF.

show abstract

The inhibition of miR-126 in cell migration and invasion of cervical cancer through regulating ZEB1

Cited by 34 publications

References 39 publications

MicroRNA‑126‑3p suppresses HeLa cell proliferation, migration and invasion, and increases apoptosis via the PI3K/PDK1/AKT pathway

MicroRNA‑126‑3p suppresses HeLa cell proliferation, migration and invasion, and increases apoptosis via the PI3K/PDK1/AKT pathway

<p><em>MiR-139-5p-ZEB1</em> is a Molecular Regulator of Growth, Invasion, and Epithelial-to-Mesenchymal Transition of Cervical Cancer</p>

Klotho antagonizes pulmonary fibrosis through suppressing pulmonary fibroblasts activation, migration, and extracellular matrix production: a therapeutic implication for idiopathic pulmonary fibrosis

Contact Info

Product

Resources

About