Long noncoding RNAs in development and cancer: potential biomarkers and therapeutic targets

Fatima, Roshan; Akhade, Vijay Suresh; Pal, Debosree; Rao, Satyanarayana M.R.

doi:10.1186/s40591-015-0042-6

Cited by 233 publications

(202 citation statements)

References 306 publications

(314 reference statements)

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“…LncRNAs are emerging as key players in different biological process, including cancer. In fact, lncRNAs have an advantage over protein-coding genes since their expression is more tissue specific, thus making them attractive as novel diagnostic tools [11]. Previously, we reported that human cells express a unique family of mitochondrial long ncmtRNAs (ncmtRNAs) [12,13].…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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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“…In addition to biochemical diversity, a common theme for lncRNA function is temporal control of gene expression, regulating cellular programs that require highly specific and well timed responses to extracellular stimuli. [28][29][30] Unsurprisingly, misregulation of lncRNAs has been linked to the development of a multitude of human diseases including cancer 31 and heart failure. 32 The budding yeast Saccharomyces cerevisiae has been a robust system for genetic and molecular investigation of gene expression steps since its introduction as a model organism almost 30 y ago.…”

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confidence: 99%

LncRNAs: Bridging environmental sensing and gene expression

2016

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The survival of all organisms is dependent on complex, coordinated responses to environmental cues. Non-coding RNAs have been identified as major players in regulation of gene expression, with recent evidence supporting roles for long non-coding (lnc)RNAs in both transcriptional and post-transcriptional control. Evidence from our laboratory shows that lncRNAs have the ability to form hybridized structures called R-loops with specific DNA target sequences in S. cerevisiae, thereby modulating gene expression. In this Point of View, we provide an overview of the nature of lncRNA-mediated control of gene expression in the context of our studies using the GAL gene cluster as a model for controlling the timing of transcription.

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“…We used a small interfering RNA (siRNA) that targeted UCA1 to normal cells, and their dysregulation could affect cell proliferation, apoptosis, autophagy, migration and metastasis. Our findings strongly suggest that lncRNAs could be used as a novel class of biomarkers as well as therapeutic targets for at least some types of cancers [22].…”

Section: The Effect Of Uca1 Inhibition On Cell Proliferation and Cellmentioning

confidence: 61%

UCA1, a long noncoding RNA, promotes the proliferation of CRC cells via p53/p21 signaling

Shen

Xiao

et al. 2016

Open Life Sciences

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Abstract:Objective: Recently, the role of long noncoding RNAs (lncRNAs) in human colorectal cancer (CRC) has been a subject of intense focus. We set out to determine the function of one lncRNA, termed urothelial carcinoma-associated 1 (UCA1) in CRC cell proliferation and its underlying mechanisms. Methods: Quantitative real-time PCR (qRT-PCR) was applied to detect the expression level of UCA1 in 50 pairs of CRC samples compared with non-tumor colon tissues. Cell growth was determined using the Cell Counting Kit-8 (CCK-8). Western blotting was carried out to analyze the related protein expression. Flow cytometry was done to evaluate cell apoptosis by UCA1 inhibition. Results: We found an increased expression of UCA1 in CRC samples. Knockdown of UCA1 in HCT116 cells induced a decrease in cell proliferation rate compared to control samples. This oncogenic activity may be enhanced through p53/ p21 signaling. Conclusion: Our results supported the hypothesis that upregulation of UCA1 contributes to the unlimited proliferation rate of CRC cells, at least partially through the negative regulation of p53/p21 signaling pathway. Finally, we found that UCA1 merely influenced CRC cell apoptosis.

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Long noncoding RNAs in development and cancer: potential biomarkers and therapeutic targets

Cited by 233 publications

References 306 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

LncRNAs: Bridging environmental sensing and gene expression

UCA1, a long noncoding RNA, promotes the proliferation of CRC cells via p53/p21 signaling

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