HPV status is associated with altered PIWI-interacting RNA expression pattern in head and neck cancer

Firmino, Natalie; Martínez, Victor D.; Rowbotham, David A.; Enfield, Katey S.S.; Bennewith, Kevin L.; Lam, Wan L.

doi:10.1016/j.oraloncology.2016.01.012

Cited by 48 publications

(44 citation statements)

References 38 publications

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“…Expression matrices were aligned to clinicopatholgical features in order to compare miRNA, piRNA, lncRNA and sn/snoRNA levels for association with specific TNBC phenotypes. Statistical analyses were carried out using the non-parametric Mann-Whitney U test followed by false discovery rate (FDR) correction through the Benjamin-Hochberg method, with the default p -value <0.05 considered statistically significant 13. A Circos plot 14 was generated for differential expression of all small RNAs.…”

Section: Methodsmentioning

confidence: 99%

A Comprehensive NGS Data Analysis of Differentially Regulated miRNAs, piRNAs, lncRNAs and sn/snoRNAs in Triple Negative Breast Cancer

Koduru¹,

Tiwari²,

Leberfinger³

et al. 2017

J. Cancer

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Cancer is the second leading cause of death in the United States and is a major public health concern worldwide. Basic, clinical and epidemiological research is leading to improved cancer detection, prevention, and outcomes. Recent technological advances have allowed unbiased and comprehensive screening of genome-wide gene expression. Small non-coding RNAs (sncRNAs) have been shown to play an important role in biological processes and could serve as a diagnostic, prognostic and therapeutic biomarker for specific diseases. Recent findings have begun to reveal and enhance our understanding of the complex architecture of sncRNA expression including miRNAs, piRNAs, lncRNAs, sn/snoRNAs and their relationships with biological systems. We used publicly available small RNA sequencing data that was derived from 24 triple negative breast cancers (TNBC) and 14 adjacent normal tissue samples to remap various types of sncRNAs. We found a total of 55 miRNAs were aberrantly expressed (p<0.005) in TNBC samples (8 miRNAs upregulated; 47 downregulated) compared to adjacent normal tissues whereas the original study reported only 25 novel miRs. In this study, we used pathway analysis of differentially expressed miRNAs which revealed TGF-beta signaling pathways to be profoundly affected in the TNBC samples. Furthermore, our comprehensive re-mapping strategy allowed us to discover a number of other differentially expressed sncRNAs including piRNAs, lncRNAs, sn/snoRNAs, rRNAs, miscRNAs and nonsense-mediated decay RNAs. We believe that our sncRNA analysis workflow is extremely comprehensive and suitable for discovery of novel sncRNAs changes, which may lead to the development of innovative diagnostic and therapeutic tools for TNBC.

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Section: Methodsmentioning

confidence: 99%

A Comprehensive NGS Data Analysis of Differentially Regulated miRNAs, piRNAs, lncRNAs and sn/snoRNAs in Triple Negative Breast Cancer

Koduru¹,

Tiwari²,

Leberfinger³

et al. 2017

J. Cancer

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“…In recent years, small non‐coding RNAs, including miRNAs, siRNAs, and piRNAs has garnered the attention of the researchers in the field of gene regulation and epigenetics . Recent studies have shown that piRNAs, a newly discovered class of ncRNAs are differentially expressed in cancers and regulate several key biological processes revealing their tumorigenic potential (tumor suppressors or oncogenes) . Hence, this class of ncRNAs has the potential to be used as diagnostic and prognostic markers as well as therapeutic interventions for different types of human cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, our lab has also reported the expression of piRNAs in human brain, and Alzheimer's disease (AD)‐affected brain, epithelial ovarian cancer sub‐types and neuroblastoma . Further, aberrant expression of piRNAs has been documented in cancers such as breast, pancreas, lung, kidney, colorectal, cervical, head, neck, and gastric cancer . However, only a few piRNAs such as piR‐651, piR‐20365, piR‐021285, piR‐932, and piR‐823 have been intensively explored and validated in different cancers to decipher their role in oncogenesis .…”

Section: Introductionmentioning

confidence: 99%

Tumor suppressive activity of PIWI‐interacting RNA in human fibrosarcoma mediated through repression of RRM2

Das

Roy

Jain

et al. 2018

Molecular Carcinogenesis

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P‐element induced wimpy testis (PIWI)‐interacting RNAs (piRNAs) are a promising class of small regulatory RNAs, earlier believed to control transposable elements (TEs) activity in germlines are now reported in somatic and cancer cells. The aberrant expression of piRNAs has been documented in various cancers wherein they modulate tumorigenesis either as oncogenes or tumor suppressors by curbing target gene expression. However, there is no report yet on the association of piRNAs in fibrosarcoma, an early metastatic lethal tumor. For the first time, we reported a piRNA, piR‐39980 in fibrosarcoma and investigated its potential role in malignancy by employing several methods such as qRT‐PCR, MTT assay, transwell invasion and migration assay, wound healing assay, flow cytometric cell cycle analysis, Annexin V‐PE apoptosis assay, AO/EB dual staining assay, and chromatin condensation assay. We observed that piR‐39980 significantly attenuated proliferation, migration, invasion, and colony forming ability as well as induced apoptotic cell death of HT1080 fibrosarcoma cells when transiently overexpressed with its piRNA mimics. The dual luciferase reporter assay confirmed that piR‐39980 promotes apoptosis and inhibits proliferation in fibrosarcoma by repressing RRM2 through direct targeting at its 3′UTR through extensive sequence complementary binding, unlike microRNA targeting. In summary, this study revealed that piR‐39980 has a strong anti‐tumor effect and hence could be a promising RNA‐based therapeutic agent for the malignancy of fibrosarcoma.

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“…Among ncRNAs, Piwi-interacting RNAs (piRNAs) have recently emerged as promising ncR-NAs which are initially reported to maintain genome stability either by post-transcriptional silencing or by histone modification and DNA-methylation of transposons in association with PIWI-proteins [Brennecke et al, 2007;Ku and Lin, 2014;Houwing et al, 2007;Castel and Martienssen, 2013;Watanabe and Lin, 2014]. These are of ß26-36 nucleotides (nts) in length characterised by a 3-terminal 2´-Omethylation and are now reported in somatic and cancer cells regulating differentiation, development, proliferation, apoptosis, invasiveness, angiogenesis, chemo-resistance and so on besides their germline functions [Bahn et al, 2015;Khurana and Theurkauf, 2010;Xiong et al, 2015;Weng et al, 2018;Firmino et al, 2016]. More specifically, only a few piRNAs such as piR-651, piR-20365, piR-021285, piR-932 and piR-823 have been reported to regulate oncogenesis of various cancers such as breast, pancreas, lung, kidney, colorectal, cervical, head, neck and gastric cancer [Zhang et al, 2013;Li et al, 2016;Cordeiro et al, 2016;Fu et al, 2015;Yin et al, 2017].…”

Section: Introductionmentioning

confidence: 99%

piR‐39980 promotes cell proliferation, migration and invasion, and inhibits apoptosis via repression of SERPINB1 in human osteosarcoma

Das

Jain

Mallick

2020

Biology of the Cell

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Background Information Piwi‐interacting RNAs (piRNAs) are a novel class of ∼23–36 nts long endogenous small non‐coding RNAs, earlier known to maintain germline genome integrity during development by regulating transposable elements. Recently, piRNAs are known to regulate cell proliferation, apoptosis and metastasis in different cancer cells. However, piRNAs have not yet been reported in human osteosarcoma (OS), a highly metastatic aggressive bone tumour among adolescents. Therefore, our current study aimed to decrypt the potential role of a piRNA, piR‐39980 in osteosarcoma, which was earlier reported by us in fibrosarcoma, neuroblastoma and epithelial ovarian cancer. Results We found that piR‐39980 is significantly upregulated in two human osteosarcoma cell lines, 143B and HOS compared to IMR90‐tert fibroblast cells. The transient overexpression of endogenous piR‐39980 level through transfection by piRNA mimic promotes proliferation, migration and invasion ability of OS cells, whereas its inhibition significantly induces apoptosis, chromatin condensation and γ‐H2AX accumulation as well as restrains migration and invasion of OS cells. Further, we found 13 genes as targets of piR‐39980 using miRanda, among which SERPINB1 that is downregulated in OS cells is seen to suppress proliferation, and migration in this cancer upon its overexpression. The knockdown of piR‐39980 in OS cells led to enhanced expression of SERPINB1 indicating to be its target, which was then confirmed by dual luciferase reporter assay. In addition, gelatin zymography and western blotting revealed that transfection of piR‐39980 mimic promotes MMP‐2 activation, whereas its inhibition and SERPINB1 overexpression suppresses MMP‐2 activation in OS cells. Conclusions Taken together, our study revealed that piR‐39980 promotes migration and invasion via MMP‐2 activation as well as inhibits cell death, both through negative regulation of SERPINB1. Significance This study revealed that piR‐39980 functions as an oncogene in human osteosarcoma, which could be harnessed as a potential therapeutic target for this malignancy.

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HPV status is associated with altered PIWI-interacting RNA expression pattern in head and neck cancer

Cited by 48 publications

References 38 publications

A Comprehensive NGS Data Analysis of Differentially Regulated miRNAs, piRNAs, lncRNAs and sn/snoRNAs in Triple Negative Breast Cancer

A Comprehensive NGS Data Analysis of Differentially Regulated miRNAs, piRNAs, lncRNAs and sn/snoRNAs in Triple Negative Breast Cancer

Tumor suppressive activity of PIWI‐interacting RNA in human fibrosarcoma mediated through repression of RRM2

piR‐39980 promotes cell proliferation, migration and invasion, and inhibits apoptosis via repression of SERPINB1 in human osteosarcoma

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