MicroRNA-182-5p and microRNA-205-5p as potential biomarkers for prognostic stratification of p16-positive oropharyngeal squamous cell carcinoma

Weiss, Bernhard G.; Anczykowski, Mahalia Zoe; Ihler, Friedrich; Bertlich, Mattis; Spiegel, Jennifer L.; Haubner, Frank; Canis, Martin; Küffer, Stefan; Heß, Julia; Unger, Kristian; Kitz, Julia; Jakob, Mark

doi:10.3233/cbm-203149

Cited by 8 publications

(7 citation statements)

References 81 publications

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“…Again intriguingly, for HPV-induced cervical cancer just the opposite mechanism, a TGF-b/Smad4-mediated increase of miR-182 has been reported and in breast cancer TGFb was described to mediate BRCAness and PARP sensitivity by induction of miR-181, which was also reported to reduce the expression of BRCA1 and ATM (15,16). Furthermore, the long isoform of miR182 (miR182-5p) was recently suggested as associated with inferior outcome in p16+ OPSCC (17).…”

Section: Introductionmentioning

confidence: 99%

A Lack of Effectiveness in the ATM-Orchestrated DNA Damage Response Contributes to the DNA Repair Defect of HPV-Positive Head and Neck Cancer Cells

et al. 2022

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Patients with human papillomavirus-positive squamous cell carcinoma of the head and neck (HPV+ HNSCC) have a favorable prognosis compared to those with HPV-negative (HPV−) ones. We have shown previously that HPV+ HNSCC cell lines are characterized by enhanced radiation sensitivity and impaired DNA double-strand break (DSB) repair. Since then, various publications have suggested a defect in homologous recombination (HR) and dysregulated expression of DSB repair proteins as underlying mechanisms, but conclusions were often based on very few cell lines. When comparing the expression levels of suggested proteins and other key repair factors in 6 HPV+ vs. 5 HPV− HNSCC strains, we could not confirm most of the published differences. Furthermore, HPV+ HNSCC strains did not demonstrate enhanced sensitivity towards PARP inhibition, questioning a general HR defect. Interestingly, our expression screen revealed minimal levels of the central DNA damage response kinase ATM in the two most radiosensitive HPV+ strains. We therefore tested whether insufficient ATM activity may contribute to the enhanced cellular radiosensitivity. Irrespective of their ATM expression level, radiosensitive HPV+ HNSCC cells displayed DSB repair kinetics similar to ATM-deficient cells. Upon ATM inhibition, HPV+ cell lines showed only a marginal increase in residual radiation-induced γH2AX foci and induction of G2 cell cycle arrest as compared to HPV− ones. In line with these observations, ATM inhibition sensitized HPV+ HNSCC strains less towards radiation than HPV− strains, resulting in similar levels of sensitivity. Unexpectedly, assessment of the phosphorylation kinetics of the ATM targets KAP-1 and Chk2 as well as ATM autophosphorylation after radiation did not indicate directly compromised ATM activity in HPV-positive cells. Furthermore, ATM inhibition delayed radiation induced DNA end resection in both HPV+ and HPV− cells to a similar extent, further suggesting comparable functionality. In conclusion, DNA repair kinetics and a reduced effectiveness of ATM inhibition clearly point to an impaired ATM-orchestrated DNA damage response in HPV+ HNSCC cells, but since ATM itself is apparently functional, the molecular mechanisms need to be further explored.

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Section: Introductionmentioning

confidence: 99%

A Lack of Effectiveness in the ATM-Orchestrated DNA Damage Response Contributes to the DNA Repair Defect of HPV-Positive Head and Neck Cancer Cells

et al. 2022

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“…In the case of ncRNAs, to the best of our knowledge only miR-205 and HOTAIR have been related with head and neck (112), and oropharyngeal cancers (113), as well as with cervicovaginal lavage specimens, respectively (114). In accordance with the aforementioned studies, the establishment of a panel of biomarkers with high sensitivity and specificity would be a great molecular tool to improve the diagnosis and treatment of women with LGCLs, HGCLs and CC.…”

Section: Expression Of Circulating Biomarkers In Other Hpvrelated Can...mentioning

confidence: 56%

Section: Expression Of Circulating Biomarkers In Other Hpv-related Ca...mentioning

confidence: 99%

Circulating cervical cancer biomarkers potentially useful in medical attention (Review)

Garrido

Gutiérrez²,

Flores

2023

Mol Clin Oncol

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Cervical cancer (CC) is a public health problem worldwide, including Mexico. This type of cancer is the fourth most frequent in women worldwide; in Mexico it is the second most common type in women after breast cancer. The diagnosis of CC is based mainly on Pap smears and colposcopy and the identification of molecular tools that serve as a support for these methods is urgent. Regarding this, differential expressions of specific circulating biomolecules has been detected and, based on this, they have been postulated as potential biomarkers for CC diagnosis, prognosis, and/or to identify the response to treatments. Importantly, the combined analysis of these molecules considerably improves their efficacy as biomarkers and their potential use in the medical attention is promising. Contents1. Introduction 2. Proteins 3. ncRNAs 4. The estrogen effect on the expression of biomarkers 5. cDNA 6. Putative molecular mechanisms altered by the CC biomarkers 7. Circulating biomarkers expression in other HPV-related cancers 8. How feasible is it to use a test of this type in the heath sector of undeveloped countries? 9. The best biomarkers panel, according to our point of view 10. Conclusions and future directions

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“…Generally, miRNAs may represent novel biomarkers in HPV-positive HNSCC. House et al (49) and Weiss et al (50) have reported that miR-205-5p, miR-182-5p, and miR-133a-3p were overexpressed in HPV-positive OPSCC, and could be adapted as prognostic markers (49)(50)(51). Bersani et al and Gougousis et al (45,51) have reported that miRNAs were correlated with distant tumor metastasis, invasion, and migration, even could discriminate tumor stages (2-4 of T stages) in HPVpositive Tongue squamous cell carcinoma (TSCC) and OPSCC.…”

Section: Expression and Significance Of Mirnas In Hpv-positive Hnsccmentioning

confidence: 99%

Expression and molecular regulation of non-coding RNAs in HPV-positive head and neck squamous cell carcinoma

Guo

Yang

et al. 2023

Front. Oncol.

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Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide. Accumulating evidence suggests that persistent HPV infection is closely related to a subset of HNSCC types, and the incidence of human papillomavirus (HPV)-positive HNSCC has been annually increasing in recent decades. Although the carcinogenesis of HPV-positive HNSCC has not been completely elucidated, it has been well confirmed that E6 and E7, the main viral oncoproteins are responsible for the maintenance of malignant transformation, promotion of cell proliferation, and increase in tumor invasion. Moreover, compared with HPV-negative HNSCC, HPV-positive HNSCC shows some special clinical-pathological features, which are possibly related to HPV infection and their specific regulatory mechanisms. Non-coding RNA (ncRNA) is a class of RNA lacking the protein-coding function and playing a critical regulatory role via multiple complex molecular mechanisms. NcRNA is an important regulatory pattern of epigenetic modification, which can exert significant effects on HPV-induced tumorigenesis and progression by deregulating downstream genes. However, the knowledge of ncRNAs is still limited, hence, a better understanding of ncRNAs could provide some insights for exploring the carcinogenesis mechanism and identifying valuable biomarkers in HPV-positive HNSCC. Therefore, in this review, we mainly focused on the expression profile of ncRNAs (including lncRNA, miRNA, and circRNA) and explored their regulatory role in HPV-positive HNSCC, aiming to clarify the regulatory mechanism of ncRNAs and identify valuable biomarkers for HPV-positive HNSCC.

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MicroRNA-182-5p and microRNA-205-5p as potential biomarkers for prognostic stratification of p16-positive oropharyngeal squamous cell carcinoma

Cited by 8 publications

References 81 publications

A Lack of Effectiveness in the ATM-Orchestrated DNA Damage Response Contributes to the DNA Repair Defect of HPV-Positive Head and Neck Cancer Cells

A Lack of Effectiveness in the ATM-Orchestrated DNA Damage Response Contributes to the DNA Repair Defect of HPV-Positive Head and Neck Cancer Cells

Circulating cervical cancer biomarkers potentially useful in medical attention (Review)

Expression and molecular regulation of non-coding RNAs in HPV-positive head and neck squamous cell carcinoma

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