Human papillomavirus 16 E6 modulates the expression of host microRNAs in cervical cancer

Ben, Wei; Yang, Yang; Yuan, Jing; Sun, Junqi; Huang, Mingli; Zhang, Dandan; Zheng, Junfang

doi:10.1016/j.tjog.2014.06.007

Cited by 27 publications

(17 citation statements)

References 29 publications

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“…There is evidence that HPV alters the expression of host cell microRNAs and the cargo of EVs released by cervical cancer cells . However, despite the common viral aetiology, there are no similar studies in OPSCC.…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicle microRNA cargo is correlated with HPV status in oropharyngeal carcinoma

Peacock

Rigby

Bradford

et al. 2018

J Oral Pathology Medicine

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Background: The incidence of human papilloma virus positive (HPV + ) oropharyngeal squamous cell carcinoma (OPSCC) has increased rapidly in recent decades. These tumours have a favourable outcome compared to HPV-negative (HPV − ) OPSCC. However, HPV + tumours are more likely to metastasise to distant sites, suggesting a difference in how these tumour subtypes interact with the metastatic niche. Extracellular vesicles (EVs) have emerged as important players in cell-to-cell communication and are a potential source of biomarkers for cancer diagnosis. This study aims to characterise the microRNA cargo of small EVs released by HPV + and HPV − OPSCC cell lines. Methods: Extracellular vesicles produced by HPV + (SCC2 and SCC90) and HPV − (SCC72 an SCC89) OPSCC cells were characterised by tunable resistive pulse sensing (TRPS) and western blotting. RNA was extracted from EVs and analysed by small RNA sequencing. A bioinformatics approach was used to identify EV miRNA signatures associated with HPV status. Results: HPV − OPSCC cells produced more EVs than HPV + OPSCC cells. EVs were positive for the common EV markers CD63, CD9 and TSG101. Unbiased hierarchical clustering analysis of EV miRNA cargo revealed that samples clustered based on HPV status. 14 miRNA were enriched in HPV + cell-derived EVs, whereas 19 miRNA were enriched in EVs derived from HPV − cell lines. Conclusions: Here, we identify EV miRNA signatures indicative of the HPV status of the parent cell. This may provide a platform from which to validate salivary or bloodbased biomarkers with utility for early detection and stratifying risk in OPSCC patients. K E Y W O R D S extracellular vesicles, head and neck cancer, human papillomavirus, microRNA, oropharyngeal carcinoma

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Section: Introductionmentioning

confidence: 99%

Extracellular vesicle microRNA cargo is correlated with HPV status in oropharyngeal carcinoma

Peacock

Rigby

Bradford

et al. 2018

J Oral Pathology Medicine

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“…Some studies also demonstrated that the expression of miR-218 was strongly downregulated by HPV E6 [14, 20], but the mechanisms of the function of HPV on miR-218 and the role of miR-218 on the metastasis of cervical cancer are not well understood. In the present study, we attempted to further explore the role of miR-218 on the metastasis of cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer

et al. 2016

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Repeated infection with high-risk HPV is a major cause for the development and metastasis of human cervical cancer, even though the mechanism of the metastasis is still not completely understood. Here, we reported that miR-218 (microRNA-218) was downregulated in cervical cancer tissues, especially in metastatic cancer tissues. We found that miR-218 expression was associated with clinicopathological characteristics of patients with cervical cancer. MiR-218 overexpression inhibited Epithelial-Mesenchymal Transition (EMT), migration and invasiveness of cervical cancer cells in vitro. Moreover, miR-218 repressed the expression of SFMFBT1 (Scm-like with four MBT domains 1) and DCUN1D1 (defective in cullin neddylation 1, domain containing 1) by direct binding to the 3′UTRs of the mRNAs. The overexpression of SFMBT1 induced EMT and increased the migration and invasiveness of cervical cancer cells, while the overexpression of DCUN1D1 increased the migration and invasiveness of these cells, but did not induce EMT. An inverse correlation was observed between the expression of miR-218 and DCUN1D1 protein in cervical cancer tissues. Importantly, HPV16 E6 downregulated the expression of miR-218 in cervical cancer, while miR-218 rescued the promotion effect of HPV16 E6 on the expression of SFMBT1 and DCUN1D1. Taken together, our results revealed that HPV16 E6 promoted EMT and invasion in cervical cancer via the repression of miR-218, while miR-218 inhibited EMT and invasion in cervical cancer by targeting SFMBT1 and DCUN1D1.

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“…Although the molecular mechanisms that regulate the spread of HPV + HNSCC remain to be explored, E6 and E7 have also been shown to increase the migration of cervical cancer cells which is thought to occur by decreasing RhoA activity . Rho GTPases are overexpressed in HNSCC, and RhoA controls actomyosin contractility to mediate cell migration .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, RhoA signaling can promote invadopodia activity . While E6 can deregulate miRNA expression to affect migration, these mechanisms are mediated by p53 which is inactivated in SCC‐25 cells . Therefore, HPV may exert its effects on Rho through additional mechanisms which alter downstream signaling important for migration and invadopodia activity.…”

Section: Discussionmentioning

confidence: 99%

Expression of human papillomavirus oncoproteins E6 and E7 inhibits invadopodia activity but promotes cell migration in HPV‐positive head and neck squamous cell carcinoma cells

2018

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Human papillomavirus 16 E6 modulates the expression of host microRNAs in cervical cancer

Abstract: Our results indicate that HPV infection and subsequent transformation take place through complex regulatory patterns of gene expression in the host cells, part of which are regulated by the E6 protein.

Cited by 27 publications

References 29 publications

Extracellular vesicle microRNA cargo is correlated with HPV status in oropharyngeal carcinoma

Extracellular vesicle microRNA cargo is correlated with HPV status in oropharyngeal carcinoma

MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer

Expression of human papillomavirus oncoproteins E6 and E7 inhibits invadopodia activity but promotes cell migration in HPV‐positive head and neck squamous cell carcinoma cells

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