A piRNA-like small RNA interacts with and modulates p-ERM proteins in human somatic cells

Mei, Yuping; Wang, Yuyan; Kumari, Priti; Shetty, Amol C.; Clark, David; Gable, Tyler; MacKerell, Alexander D.; Mark, Z.; Weber, David J.; Yang, Austin J.; Edelman, Martin J.; Li, Mao

doi:10.1038/ncomms8316

Cited by 96 publications

(120 citation statements)

References 62 publications

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“…Previous works demonstrated that in silico prediction tools [13] allowed to identify new, non-annotated, piRNAs that were then experimentally validated and found to exert important biological activities [14]. Non annotated 21–35 nt long reads from all smallRNA-Seq datasets of CN and HCC samples, generated as described above and first analyzed for known piRNAs, were thus searched for novel piRNAs as described by Mei et al [14].…”

Section: Resultsmentioning

confidence: 99%

Specific patterns of PIWI-interacting small noncoding RNA expression in dysplastic liver nodules and hepatocellular carcinoma

et al. 2016

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Hepatocellular carcinoma (HCC) is the result of a stepwise process, often beginning with development within a cirrhotic liver of premalignant lesions, morphologically characterized by low- (LGDN) and high-grade (HGDN) dysplastic nodules. PIWI-interacting RNAs (piRNAs) are small noncoding RNAs (sncRNAs), 23–35 nucleotide-long, exerting epigenetic and post-transcriptional regulation of gene expression. Recently the PIWI-piRNA pathway, best characterized in germline cells, has been identified also in somatic tissues, including stem and cancer cells, where it influences key cellular processes.Small RNA sequencing was applied to search for liver piRNAs and to profile their expression patterns in cirrhotic nodules (CNs), LGDN, HGDN, early HCC and progressed HCC (pHCC), analyzing 55 samples (14 CN, 9 LGDN, 6 HGDN, 6 eHCC and 20 pHCC) from 17 patients, aiming at identifying possible relationships between these sncRNAs and liver carcinogenesis. We identified a 125 piRNA expression signature that characterize HCC from matched CNs, correlating also to microvascular invasion in HCC. Functional analysis of the predicted RNA targets of deregulated piRNAs indicates that these can target key signaling pathways involved in hepatocarcinogenesis and HCC progression, thereby affecting their activity. Interestingly, 24 piRNAs showed specific expression patterns in dysplastic nodules, respect to cirrhotic liver and/or pHCC.The results demonstrate that the PIWI-piRNA pathway is active in human liver, where it represents a new player in the molecular events that characterize hepatocarcinogenesis, from early stages to pHCC. Furthermore, they suggest that piRNAs might be new disease biomarkers, useful for differential diagnosis of dysplastic and neoplastic liver lesions.

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Section: Resultsmentioning

confidence: 99%

Specific patterns of PIWI-interacting small noncoding RNA expression in dysplastic liver nodules and hepatocellular carcinoma

et al. 2016

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“…For instance, piRNAs regulated Piwi protein Miwi ubiqutination by enhancing Miwi interaction with an APC/C substrate-binding subunit during late mouse spermatogenesis [17]. Mei et al [55] identified 555 piRNAs in human lung bronchial epithelial (HBE) and non-small cell lung cancer (NSCLC) cell lines. The results indicated that 295 piRNAs were novel piRNA-like sncRNAs or piRNA-Ls.…”

Section: Introductionmentioning

confidence: 99%

PIWI Proteins and PIWI-Interacting RNA: Emerging Roles in Cancer

Han

Xia

et al. 2017

Cell Physiol Biochem

127

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P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a type of noncoding RNAs (ncRNAs) and interact with PIWI proteins. piRNAs were primarily described in the germline, but emerging evidence revealed that piRNAs are expressed in a tissue-specific manner among multiple human somatic tissue types as well and play important roles in transposon silencing, epigenetic regulation, gene and protein regulation, genome rearrangement, spermatogenesis and germ stem-cell maintenance. PIWI proteins were first discovered in Drosophila and they play roles in spermatogenesis, germline stem-cell maintenance, self-renewal, retrotransposons silencing and the male germline mobility control. A growing number of studies have demonstrated that several piRNA and PIWI proteins are aberrantly expressed in various kinds of cancers and may probably serve as a novel biomarker and therapeutic target for cancer treatment. Nevertheless, their specific mechanisms and functions need further investigation. In this review, we discuss about the biogenesis, functions and the emerging role of piRNAs and PIWI proteins in cancer, providing novel insights into the possible applications of piRNAs and PIWI proteins in cancer diagnosis and clinical treatment.

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“…We recently reported, for the first time, that PIWI-interacting RNA likes (piR-Ls), a type of functional small non-coding RNAs (sncRNAs), played critical roles in NSCLC tumorigenesis and differentiation 10 . We have profiled piR-Ls expression in normal human bronchial epithelial (HBE) and NSCLC cells, and we found that LSCC, LADC, and HBE cells could be clearly clustered together on the expression patters of all piR-Ls 10 .…”

Section: Introductionmentioning

confidence: 99%

A piRNA-like Small RNA Induces Chemoresistance to Cisplatin-Based Therapy by Inhibiting Apoptosis in Lung Squamous Cell Carcinoma

Wang

Gable

Mark

et al. 2017

Molecular Therapy - Nucleic Acids

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Lung cancer is the leading cause of cancer-related death worldwide. Although advanced drugs have benefitted patients, therapeutic success has largely been hampered because of rapid development of resistance. Here we report that PIWI-interacting RNA likes (piR-Ls), a novel type of functional sncRNAs, play key roles in chemoresistance to cisplatin (CDDP)-based chemotherapy in lung squamous cell carcinoma (LSCC). piR-L-138 was upregulated upon CDDP-based chemotherapy both in LSCC cells and in patient-derived xenograft (PDX) LSCC models. Further, targeting upregulated piR-L-138 led to increased apoptosis in CDDP-treated LSCC cells and LSCC xenograft mice treated with CDDP. In addition, piR-L-138 directly interacted with p60-MDM2 and inhibited CDDP-activated apoptosis in p53-mutated LSCC. We identified the upregulated piR-L-138 upon CDDP-based chemotherapy, confirmed the enhanced sensitivity of LSCC to agents by targeting the upregulated piR-L-138 both in vitro and in vivo, and revealed mechanisms underlying piR-L-138 in chemoresistance, bolstering a new emerging clinical modality where novel functional piR-Ls provide potential strategies to overcome chemoresistance for patients with LSCC.

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A piRNA-like small RNA interacts with and modulates p-ERM proteins in human somatic cells

Cited by 96 publications

References 62 publications

Specific patterns of PIWI-interacting small noncoding RNA expression in dysplastic liver nodules and hepatocellular carcinoma

Specific patterns of PIWI-interacting small noncoding RNA expression in dysplastic liver nodules and hepatocellular carcinoma

PIWI Proteins and PIWI-Interacting RNA: Emerging Roles in Cancer

A piRNA-like Small RNA Induces Chemoresistance to Cisplatin-Based Therapy by Inhibiting Apoptosis in Lung Squamous Cell Carcinoma

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