Determination of the differential expression of mitochondrial long non-coding RNAs as a noninvasive diagnosis of bladder cancer

Rivas, Alexis; Burzio, Verónica A.; Landerer, Eduardo; Borgna, Vincenzo; Gatica, Sebastián; Ávila, Rodolfo Esteban; López, Constanza; Villota, Claudio; Fuente, Rodrigo de la; Echenique, Javiera; Burzio, Luis O.; Villegas, Jaime

doi:10.1186/1471-2490-12-37

Cited by 32 publications

(22 citation statements)

References 29 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: Discussionmentioning

confidence: 74%

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: Discussionmentioning

confidence: 74%

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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“…The main risk factors are smoking, which increase the risk up to six times, and occupational and environmental exposure to carcinogens [4,5]. About 90 % of bladder cancer corresponds to transitional cell carcinoma (TCC) [1,6] due to the fact that urothelium is constantly exposed to potential carcinogens [7]. The tumor invasiveness of TCC defines the patient's prognosis.…”

Section: Introductionmentioning

confidence: 99%

NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

Rockenbach

Braganhol

Dietrich

et al. 2014

Purinergic Signalling

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According to the World Health Organization, bladder cancer is the seventh most common cancer among men in the world. The current treatments for this malignancy are not efficient to prevent the recurrence and progression of tumors. Then, researches continue looking for better therapeutic targets which can end up in new and more efficient treatments. One of the recent findings was the identification that the purinergic system was involved in bladder tumorigenesis. The ectonucleotidases, mainly ecto-5′-nucleotidase/CD73 have been revealed as new players in cancer progression and malignity. In this work, we investigated the NTPDase3 and ecto-5′-nucleotidase/CD73 expression in cancer progression in vivo. Bladder tumor was induced in mice by the addition of 0.05 % of N-butyl-N-(hydroxybutyl)-nitrosamine (BBN) in the drinking water for 4, 8, 12, 18, and 24 weeks. After this period, mice bladders were removed for histopathology analysis and immunofluorescence assays. The bladder of animals which has received BBN had alterations, mainly inflammation, in initial times of tumor induction. After 18 weeks, mice's bladder has developed histological alterations similar to human transitional cell carcinoma. The cancerous urothelium, from mice that received BBN for 18 and 24 weeks, presented a weak immunostaining to NTPDase3, in contrast to an increased expression of ecto-5′-nucleotidase/CD73. The altered expression of NTPDase3 and ecto-5′-nucleotidase/ CD73 presented herein adds further evidence to support the idea that alterations in ectonucleotidases are involved in bladder tumorigenesis and reinforce the ecto-5′-nucleotidase/ CD73 as a future biomarker and/or a target for pharmacological therapy of bladder cancer.

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“…One of these transcripts, SncmtRNA-1, has been characterized as a regulator of cell cycle progression, while two others, ASncmtRNA-1 and 2, have been suggested to act as three tumor suppressors. Expression of SncmtRNA-2 might contribute to the screening of early cervical intraepithelial lesions [172].…”

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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Determination of the differential expression of mitochondrial long non-coding RNAs as a noninvasive diagnosis of bladder cancer

Cited by 32 publications

References 29 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

NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

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

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