Expression of Mitochondrial Non-coding RNAs (ncRNAs) Is Modulated by High Risk Human Papillomavirus (HPV) Oncogenes

Villota, Claudio; Campos, América; Vidaurre, Soledad; Oliveira-Cruz, Luciana; Boccardo, Enrique; Burzio, Verónica A.; Varas, Manuel; Villegas, Jaime; Villa, Luisa L.; Valenzuela, Pablo; Socías, Miguel; Roberts, Sally; Burzio, Luis O.

doi:10.1074/jbc.m111.326694

Cited by 51 publications

(74 citation statements)

References 64 publications

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“…The exception of the characteristic stages of cervical cancer progression is represented by the non-tumoral group, where a down-regulation of AS-mtncRNA is also evidenced. However, in the case of a true normal proliferative condition, represented by the raft model, expression of both ncmtRNAs was observed, according to previous results in different models, including cervix [13,29,30].…”

Section: Discussionsupporting

confidence: 79%

Assessment of the Expression of Long Noncoding Mitochondrial RNAs (lncmtRNAs) During Cervical Cancer Progression and Cervical Carcinoma

Dadlani¹,

López²,

Fern³

et al. 2016

J Cancer Sci Ther

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Objective: Cervical cancer is the second most common cancer in women with high rates of mortality worldwide. Cervical cancer is slowly progressive and is preceded by pre-invasive intraepithelial lesions. Therefore, detection of premalignant lesions is key to preventing disease progression to advanced stages. The objective of the present study was examination and quantification of the differentially expressed non-coding mitochondrial RNAs during progression of disease. Material and methods:The differential expression of S-ncmtRNA and AS-ncmtRNA was analyzed by in situ hybridization (ISH) using tissue macroarrays (TMA) from normal, CIN1, CIN2, CIN3 and invasive squamous carcinoma (SCC). PCNA and p16INK-4a were detected in consecutive biopsies by immunohistochemistry. Quantification of ISH signal was carried out with Image ProPlus 6.1 software and the results were expressed as percentage of Integrated Optical Density (IOD). Results:We found a marked down-regulation of AS-ncmtRNA in 95% of tissues analyzed (CIN 1/2, CIN 3, and invasive squamous cancer). Moreover, differential expression of ASncmtRNA v/s S-ncmtRNA showed significant difference. Normal proliferating tissues did not display down-regulation of AS-ncmtRNA. Down regulation of ASncmtRNA correlated with the expression of the tumor suppressor protein p16INK-4a Conclusions:We found down-regulation of AS-ncmtRNA in pre-malignant and tumor samples which could distinguish normal tissues from early lesions and tumor samples. These results suggest that the down-regulation of AS-ncmtRNA is a novel marker of early lesions and cervix neoplasia. Previously, we reported that human cells express a unique family of mitochondrial long ncmtRNAs (ncmtRNAs) [12,13]. One of these transcripts, named sense ncmtRNA (SncmtRNA) is expressed in normal proliferating cells and tumor cells but not in resting cells, suggesting a functional role in cell cycle progression [12]. Normal proliferating cells express, in addition to the S-ncmtRNA, two antisense mitochondrial ncmtRNAs (AS-ncmtRNA-1 and AS-ncmtRNA-2) where both AS-ncmtRNAs are down-regulated in human cancer cells regardless of tissue of origin. In order to analyze the expression pattern of these ncmtRNAs in cervical cancer, we performed a qualitative pilot study in cervical biopsies encompassing the progression of the disease. We found that AS-ncmtRNAs are down-regulated in mild, moderate and severe neoplasia and in invasive cervical carcinoma [14]. In the present study a quantitative analysis of the differential expression of the S-ncmtRNA and the ASncmtRNAs was performed in biopsies of CIN1 to CIN3 and invasive cervical carcinoma, correlating it with the expression of the tumor suppressor p16 Assessment of the Expression of LongINK 4A and proliferating cell nuclear antigen (PCNA). Methods Tissue specimensAll the tissues were purchased from Pantomics Inc. (Richmond, CA, USA), corresponding to Tissue Macroarrays (TMA) containing normal cervix, CIN1, CIN2, CIN3 and invasive squamous carcinoma (SCC). For normal specimens,...

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Section: Discussionsupporting

confidence: 79%

Assessment of the Expression of Long Noncoding Mitochondrial RNAs (lncmtRNAs) During Cervical Cancer Progression and Cervical Carcinoma

Dadlani¹,

López²,

Fern³

et al. 2016

J Cancer Sci Ther

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“…Other host lncRNAs, such as MALAT1, could also be used as prognosis biomarkers for several cancers, independently of viral infection. Finally, long noncoding mitochondrial RNAs (ncmtRNAs) were recently reported as deregulated following human papillomavirus (HPV) infection [171]. The expression profile of these transcripts allows researchers to distinguish between normal, pre-tumoral, and cancer cells.…”

Section: Resultsmentioning

confidence: 99%

Noncoding RNA Expression During Viral Infection: The Long and the Short of It

Josset

Tisoncik-Go

Katze

2014

MicroRNAs and Other Non-Coding RNAs in Inflammation

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New technologies have expanded our view of viral-host interactions with the growing identification of non-coding RNAs (ncRNAs) that act as key regulators of viral infection. In this chapter, we explore novel genomics-based approaches used to characterize ncRNAs involved in viral infection, focusing mainly on microRNAs and long noncoding RNAs. We present recent evidence implicating virally encoded and host-derived ncRNAs in viral replication and pathogenesis regulation, focusing on four different viral diseases (IAV, KHSV, HIV, and HBV). Finally, we discuss the current knowledge of ncRNAs modulation of innate and adaptive immune responses to viral infection. These findings highlight the complexity of host-pathogen networks determining the outcome of viral disease. Understanding the role of ncRNAs in these networks may offer novel antiviral therapy and diagnostic tools.

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“…86 HPV proteins can also induce SncmtRNA-1 and -2 expression and downregulate ASncmtRNA-1 and -2 mitochondrial lncRNAs transcript levels. [87][88][89] ASncmtRNA-1 and -2 were shown to have a decreased expression in early cervical carcinoma, 90 whereas ASncmtRNA-2 is induced in aging in endothelial cells, where it appears to affect replicative senescence by possibly participating in the cell cycle arrest in G2/M phase. 91 On the other hand, SncmtRNA-1 correlation with cell proliferation suggests a function for this transcript in cell cycle progression.…”

Section: Hpv and Lncrnamentioning

confidence: 99%

Long Noncoding RNAs in HPV-Induced Oncogenesis

Goedert¹,

Plaça²,

Nunes³

et al. 2016

Advances in Tumor Virology

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Long noncoding RNAs (lncRNAs) play important roles in a wide range of oncogenic processes, including malignant transformation, epigenetic reprogramming, epithelial-to-mesenchymal transition, and metastasis development. LncRNAs induced by oncogenic viral proteins were shown to play critical roles in tumor initiation and progression. Despite this, little is known about Human papillomavirus (HPV)-induced modulation of host's lncRNAs. In this review, we gathered published information about altered lncRNAs upon HPV status (infection/protein activity), making use of descriptive research works and published gene expression microarray experiments. A diversity of lncRNAs demonstrated to be altered, including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), H19, and maternally expressed gene 3 (MEG3). Their functions in several cancers were reviewed, indicating that they may represent potential candidates for future research on HPV-induced oncogenesis.KEY WORDS: human papillomavirus, lncRNA, cancer, ncRNA, virus CITATION: goedert et al. long noncoding rnAs in HPv-induced oncogenesis.

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Expression of Mitochondrial Non-coding RNAs (ncRNAs) Is Modulated by High Risk Human Papillomavirus (HPV) Oncogenes

Cited by 51 publications

References 64 publications

Assessment of the Expression of Long Noncoding Mitochondrial RNAs (lncmtRNAs) During Cervical Cancer Progression and Cervical Carcinoma

Assessment of the Expression of Long Noncoding Mitochondrial RNAs (lncmtRNAs) During Cervical Cancer Progression and Cervical Carcinoma

Noncoding RNA Expression During Viral Infection: The Long and the Short of It

Long Noncoding RNAs in HPV-Induced Oncogenesis

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