piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma

H, Yan; Ql, Wu; Sun, Chao; Ls, Ai; Deng, Jun; Zhang, Li; Chen, L; Zb, Chu; Tang, Borui; Wang, K; Xf, Wu; Xu, Jian; Hu, Yuantai

doi:10.1038/leu.2014.135

Cited by 190 publications

(179 citation statements)

References 55 publications

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“…Correspondingly, piRNAs have important roles in mRNA regulation in the mouse by rendering targeting specificity (6,43). Furthermore, some previous researchers suggested that piRNAs have independent functions, such as piR-823 having a role in breast cancer (5). Our analysis indicates that a small number of piRNAs are expressed in MDA-MB-231 cells.…”

Section: Discussionmentioning

confidence: 69%

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The Role of PIWIL4, an Argonaute Family Protein, in Breast Cancer

Wang

Liu

Shi

et al. 2016

Journal of Biological Chemistry

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P-element-induced wimpy testis (PIWI) proteins bind to PIWI-interacting RNAs and play key roles in the biogenesis and functions of PIWI-interacting RNAs. It has been reported that PIWI proteins are essential for stem cell self-renewal and germline development in diverse organisms and that they are ectopically expressed in multiple forms of cancer. However, the role of PIWI in cancer remains elusive. Here we report that one of the four PIWI proteins in humans, PIWIL4, is highly expressed in both breast cancer tissues and the cytoplasm of MDA-MB-231 cells derived from breast cancer. Reducing PIWIL4 expression drastically impairs the migration ability of MDA-MB-231 cells, significantly increases their apoptosis, and mildly affects their proliferation. Our transcriptome and proteome analysis reveal that these functions are at least partially achieved via the PIWIL4 regulation of TGF-␤ and FGF signaling pathways and MHC class II proteins. These findings suggest that PIWIL4 may serve as a potential therapeutic target for breast cancer.PIWI 5 proteins represent a subfamily of the Argonaute (Ago) protein family and are highly conserved among eukaryotes and archaea. PIWI proteins bind to a class of non-coding small RNAs called PIWI-interacting RNAs (piRNAs) (1-4). The PIWI-piRNA complex regulates gene expression at epigenetic and posttranscriptional levels (5-8). PIWI proteins and piRNAs are mostly expressed in the germ line, where PIWI proteins have been demonstrated to be essential for germ line development, stem cell self-renewal, and gametogenesis in diverse organisms (4, 9 -14). In addition, there is increasing evidence for somatic expression of PIWI proteins in Drosophila and mouse tissues (14 -16). Furthermore, it has been reported that PIWI proteins have aberrant and ectopic expression in a wide spectrum of cancers (17-23). For example, PIWIl2 is highly expressed in breast cancer (24). Hence, PIWI might be involved in cancer formation and/or progression.Breast cancer comprises four subtypes based on the expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor (HER2). Triple-negative breast cancer (TNBC) lacks estrogen receptor, progesterone receptor, and HER2 expression (25-27), represents ϳ10 -25% of all breast cancers, and is a clinical therapy hot spot because of the vulnerability of younger women to this subtype of breast cancer (28). Furthermore, TNBC patients do not benefit from targeted treatments such as endocrine therapy or trastuzumab because this subtype of cancer lacks the appropriate targets for these drugs. These challenges point to the pressing need to identify pathogenic pathways in TNBC. Recent studies have identified genetic alterations and gene expression profiles associated with subtypes of TNBC, including the implication of the PI3K/Akt/mTOR (mechanistic target of rapamycin) pathway in TNBC (29 -32). However, therapeutic blockade of this pathway with the PI3K/Akt/mechanistic target of rapamycin inhibitor has not been effective, indicating the existenc...

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Section: Discussionmentioning

confidence: 69%

“…liush@shanghaitech.edu.cn. 5 The abbreviations used are: PIWI, P-element-induced wimpy testis; piRNA, PIWI-interacting RNA; TNBC, triple-negative breast cancer; miRNA, microRNA. …”

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confidence: 99%

The Role of PIWIL4, an Argonaute Family Protein, in Breast Cancer

Wang

Liu

Shi

et al. 2016

Journal of Biological Chemistry

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“…However, few literatures are available. piR-823 was found to contribute to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma [66]. piR-932 was suggested to bind PIWIL2 to promote the methylation of Latexin in breast cancer stem cells [61].…”

Section: Piwi-interacting Rnas Are Related To Tumorigenesismentioning

confidence: 99%

Emerging roles for PIWI proteins in cancer

Tan¹,

Liu²,

Liao³

et al. 2015

ABBS

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It is generally accepted that PIWI proteins are predominately expressed in the germline but absent in somatic tissues. Their best-characterized role is to suppress transposon expression, which ensures genomic stability in the germline. However, increasing evidence has suggested that PIWI proteins are linked to the hallmarks of cancer defined by Weinberg and Hanahan, such as cell proliferation, anti-apoptosis, genomic instability, invasion and metastasis. This provides new possibilities for anticancer therapies through the targeting of PIWI proteins, which may have fewer side effects due to their potential classification as a CTA (cancer/testis antigen). Furthermore, PIWI has been proposed to act as a diagnostic and prognostic marker for many types of cancer, and even to differentiate early-and late-stage cancers. We herein summarize the latest progress in this exciting field, hoping to encourage new investigations of PIWIs in cancer biology that will help to develop new therapeutics for clinical application.

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“…The inhibited expression of piRNA-823 in MM cells significantly reduced DNMT3A and 3B at both mRNA and protein levels, which in turn led to decrease in global DNA methylation and reexpression of methylation-silenced tumor suppressor, p16INK4A. In addition, piRNA-823 abrogation in MM cells reduced vascular endothelial growth factor secretion, accompanied by decreased proangiogenic activity, suggesting an oncogenic role of piRNA-823 in the biology of MM [77]. Jacobs et al [78] utilized directly measured and imputed genotypes from the GliomaScan genome-wide association study (GWAS) to analyze piRNAs associated with glioma risk and the results revealed that piR-598 impacted cell survival and reduced glioma cell viability and colony formation, which sharply promoted cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

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

Han

Xia

et al. 2017

Cell Physiol Biochem

124

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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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piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma

Cited by 190 publications

References 55 publications

The Role of PIWIL4, an Argonaute Family Protein, in Breast Cancer

The Role of PIWIL4, an Argonaute Family Protein, in Breast Cancer

Emerging roles for PIWI proteins in cancer

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

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