The Role of MicroRNAs in the Metastatic Process of High-Risk HPV-Induced Cancers

Santos, Julia M.; Silva, Sara Peixoto da; Costa, Natália R.; Costa, Rui M. Gil da; Medeiros, Rui

doi:10.3390/cancers10120493

Cited by 39 publications

(22 citation statements)

References 121 publications

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“…Nuclei were visualised using DAPI (blue). Images were acquired using identical PLOS PATHOGENS miR-18a is upregulated in HPV+ cervical cancer and directly targets STK4 mRNA Both HPV E6 and E7 can modulate the microRNA (miRNA) network as a mechanism to control host gene expression [35][36][37]. The oncomiR miR-18a, a member of the oncogenic miR-17-92 cluster, is highly expressed in cervical cancer and has been shown to contribute to the proliferative and invasive phenotype, through ill-defined mechanisms [38,39].…”

Section: Fig 3 Inhibition Of Stk4/3 Kinase Activity Prevents the Blomentioning

confidence: 99%

MicroRNA-18a targeting of the STK4/MST1 tumour suppressor is necessary for transformation in HPV positive cervical cancer

et al. 2020

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Human papillomaviruses (HPV) are a major cause of malignancy worldwide. They are the aetiological agents of almost all cervical cancers as well as a subset of other anogenital and head and neck cancers. Hijacking of host cellular pathways is essential for virus pathogenesis; however, a major challenge remains to identify key host targets and to define their contribution to HPV-driven malignancy. The Hippo pathway regulates epithelial homeostasis by down-regulating the function of the transcription factor YAP. Increased YAP expression has been observed in cervical cancer but the mechanisms driving this increase remain unclear. We found significant down-regulation of the master Hippo regulatory kinase STK4 (also termed MST1) in cervical disease samples and cervical cancer cell lines compared with healthy controls. Re-introduction of STK4 inhibited the proliferation of HPV positive cervical cells and this corresponded with decreased YAP nuclear localization and decreased YAP-dependent gene expression. The HPV E6 and E7 oncoproteins maintained low STK4 expression in cervical cancer cells by upregulating the oncomiR miR-18a, which directly targeted the STK4 mRNA 3'UTR. Interestingly, miR-18a knockdown increased STK4 expression and activated the Hippo pathway, significantly reducing cervical cancer cell proliferation. Our results identify STK4 as a key cervical cancer tumour suppressor, which is targeted via miR-18a in HPV positive tumours. Our study indicates that activation of the Hippo pathway may offer a therapeutically beneficial option for cervical cancer treatment.

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Section: Fig 3 Inhibition Of Stk4/3 Kinase Activity Prevents the Blomentioning

confidence: 99%

MicroRNA-18a targeting of the STK4/MST1 tumour suppressor is necessary for transformation in HPV positive cervical cancer

et al. 2020

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“…many miRNAs are related to the occurrence, development and spread of cancer. 22,23 miRNA, as a key regulator, is involved in almost all cellular processes in mammals and other multicellular organisms, regardless of its carcinogenic or anticancer roles. 20 Current studies 24 have shown that various types of malignant tumors are associated with miRNA disorders, and about 50% of the known human miRNA are susceptible to cancer.…”

Section: Discussionmentioning

confidence: 99%

<p>Effects of Wnt/β-Catenin Signal Pathway Regulated by miR-342-5p Targeting CBX2 on Proliferation, Metastasis and Invasion of Ovarian Cancer Cells</p>

Dou¹,

Chen²,

Lu³

et al. 2020

CMAR

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Objective: This study aimed to investigate the effect of Wnt/β-catenin signal pathway mediated by miR-342-5p targeting CBX2 gene on the proliferation, metastasis, invasion and apoptosis of ovarian cancer cells, and to explore its related regulatory mechanism. Methods: Human normal ovarian epithelial cell line IOSE80, human ovarian cancer cell line SKOV3 and OVCAR3 were the subjects. Software were used to predict the binding site of miR-342-5p targeting CBX2 gene. The proliferation rate of ovarian cancer cells was detected by MTT method; the cell viability of each group was observed by colony formation test; the apoptosis of cells in each group was detected by flow cytometry; the invasive ability of cells was determined by transwell test, and the migration ability of cells was detected by scratch test. The mRNA expression levels of miR-342-5p, CBX2, Wnt1, β-catenin, C-myc and Cyclin D1 were measured by qRT-PCR. Also, Western blot was used to determine the protein expression levels of CBX2, Wnt1, β-catenin, C-myc and Cyclin D1. Results: CBX2 was identified as the target gene of miR-342-5p. MTT test results showed that miR-342-5p could significantly inhibit the proliferation of SKOV3 and OVCAR3 cells, colony formation assay results indicated that the viability of SKOV3 and OVCAR3 cells transfected with miR-342-5p decreased significantly, and flow cytometry results suggested that miR-342-5p could promote the apoptosis of SKOV3 and OVCAR3 cells. Also, the results of transwell showed that miR-342-5p could significantly inhibit the invasive ability of SKOV3 and OVCAR3 cells, and the results of scratch assay suggested that miR-342-5p could significantly inhibit the migration of SKOV3 and OVCAR3 cells. Moreover, qRT-PCR and Western blot results indicated that the mRNA and protein expression levels of CBX2, Wnt1, β-catenin, C-myc and Cyclin D1 decreased in SKOV3 and OVCAR3 cells transfected with miR-342-5p, while the mRNA expression levels of miR-342-5p increased significantly (P<0.05). Conclusion: MiR-342-5p targeted gene is CBX2, which can significantly reduce the proliferation, invasion, migration and viability of ovarian cancer cell lines SKOV3 and OVCAR3, and promote their apoptosis. The mechanism may be related to the mediation of Wnt/β-catenin signal pathway and down-regulation of the related genes expression.

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“…Overexpression of E6/E7 promotes genetic instability and chromosomal rearrangements that enhance the risk of integration [46]. Similarly, deregulation of viral gene expression deregulates the cell cycle via p53 and Rb degradation, deregulation of oncogenes and miRNAs expression [[47], [48], [49], [50]]. Without a doubt, further investigation is required to determine the detailed mechanisms of HPV-induced cervical cancer.…”

Section: Systems Biology Approaches In Cervical Cancermentioning

confidence: 99%

Recent Advances on the Molecular Mechanism of Cervical Carcinogenesis Based on Systems Biology Technologies

Lin

Zhou

et al. 2019

Computational and Structural Biotechnology Journal

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Cervical cancer is one of the common malignancies in women worldwide. Exploration of pathogenesis and molecular mechanism of cervical cancer is pivotal for development of effective treatment for this disease. Recently, systems biology approaches based on high-throughput technologies have been carried out to investigate the expression of some genes and proteins in genomics, transcriptomics, proteomics, and metabonomics of cervical cancer. Compared with traditional methods，systems biology technology has been shown to provide large of information regarding prognostic biomarkers and therapeutic targets for cervical cancer. These molecular signatures from system biology technology could be useful to understand the molecular mechanisms of cervical cancer development and progression, and help physicians to design targeted therapeutic strategies for patients with cervical cancer.

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The Role of MicroRNAs in the Metastatic Process of High-Risk HPV-Induced Cancers

Cited by 39 publications

References 121 publications

MicroRNA-18a targeting of the STK4/MST1 tumour suppressor is necessary for transformation in HPV positive cervical cancer

MicroRNA-18a targeting of the STK4/MST1 tumour suppressor is necessary for transformation in HPV positive cervical cancer

<p>Effects of Wnt/β-Catenin Signal Pathway Regulated by miR-342-5p Targeting CBX2 on Proliferation, Metastasis and Invasion of Ovarian Cancer Cells</p>

Recent Advances on the Molecular Mechanism of Cervical Carcinogenesis Based on Systems Biology Technologies

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