piR-651 promotes tumor formation in non-small cell lung carcinoma through the upregulation of cyclin D1 and CDK4

Li, Dan; Luo, Yuan; Gao, Yawen; Yang, Yue; Wang, Yina; Xu, Yan; Tan, Shuhua; Zhang, Yuwei; Duan, Juan; Yu, Yang

doi:10.3892/ijmm.2016.2671

Cited by 74 publications

(64 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression of piR651 significantly increases in non-small cell lung carcinoma [26] and piRNA823 is overexpressed in multiple myeloma patients [27]. Hence, it is possible that HIWI2-associated piRNAs might also be altered in RB and could play a role in the pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

PIWI-like protein, HIWI2 is aberrantly expressed in retinoblastoma cells and affects cell-cycle potentially through OTX2

Sivagurunathan

Chidambaram

2017

Cell Mol Biol Lett

View full text Add to dashboard Cite

Retinoblastoma (RB), a childhood cancer, is caused by biallelic mutation of the RB1 gene, but its development is not clearly understood. Furthermore, the presence of a cancer stem cell subpopulation in RB might impact its treatment. PIWI protein, known for its role in stem cell self-renewal, is aberrantly expressed in cancers. We examined the role of the PIWI-like protein HIWI2 in RB and its effect on the stem cell markers in cells of the RB line, Y79. The expression of HIWI2 is significantly increased in Y79 compared with its level in HeLa and ARPE19 cells. The stem cell markers Oct-3/4, Nanog and Sox-2 were not altered upon HIWI2 knockdown in Y79 cells. Interestingly, OTX2 was significantly downregulated in the absence of HIWI2. Otx2 transcripts also decreased in HIWI2-silenced Y79 and ARPE19 cells. Moreover, silencing HIWI2 in Y79 accumulated the cells at G2–M phase and reduced the levels of proliferating cell nuclear antigen (PCNA) and the tumor suppressor, p16. Our results demonstrate that HIWI2 is aberrantly expressed in Y79 cells and silencing of HIWI2 downregulates OTX2, suggesting that HIWI2 might play a role in the progression of RB.

show abstract

Section: Discussionmentioning

confidence: 99%

PIWI-like protein, HIWI2 is aberrantly expressed in retinoblastoma cells and affects cell-cycle potentially through OTX2

Sivagurunathan

Chidambaram

2017

Cell Mol Biol Lett

View full text Add to dashboard Cite

show abstract

Section: Piwi-pirna In Cancer Developmentmentioning

confidence: 99%

“…A specific piRNA-651 has been demonstrated to be aberrantly overexpressed in various tumors compared with in wild-type tissues (58,59). In NSCLC, a significant increase in piRNA-651 levels was identified to be associated with cancer progression (58). Furthermore, the upregulation of piRNA-651 in A549 lung cancer cells caused a significant increase in cell viability and metastasis, and was associated with the upregulation of cyclin D1 and CDK4 in vivo and in vitro .…”

Section: Piwi-pirna In Cancer Developmentmentioning

confidence: 99%

“…The level of piRNA-823 was positively associated with tumor lymph node metastasis and distant metastasis (60). Conversely, upregulated expression of piRNA-651 was observed in gastric, colon, lung and breast cancer tissues (58–60). Increased levels of piRNA-4987, −20365, −20485 and −20582 were observed in breast tumors compared with in non-cancerous tissues, and were associated with lymph node metastasis (60).…”

Section: Piwi-pirna In Cancer Developmentmentioning

confidence: 99%

See 1 more Smart Citation

The meaning of PIWI proteins in cancer development

et al. 2017

View full text Add to dashboard Cite

Abstract. Cancer is a histologically and genetically heterogeneous population of tumor cells that exhibits distinct molecular profiles determined by epigenetic alterations. P-element-induced wimpy testis (PIWI) proteins in complex with PIWI-interacting RNA (piRNA) have been previously demonstrated to be involved in epigenetic regulation in germline cells. Recently, reactivation of PIWI expression, primarily PIWI-like protein 1 and 2, through aberrant DNA methylation resulting in genomic silencing has been identified in various types of tumors. It has been suggested that the PIWI-piRNA complex contributes to cancer development and progression by promoting a stem-like state of cancer cells, or cancer stem cells (CSCs). It has been identified that CSCs represent the cells that have undergone epithelial-mesenchymal transition (EMT) and acquired metastatic capacities. However, the molecular association between the EMT process and the stem-cell state remains unclear. Further extensive characterization of CSCs in individual types of tumors is required to identify specific markers for the heterogeneous population of CSCs and therefore selectively target CSCs. Previous studies indicate a reciprocal regulation between PIWI proteins and a complex signaling network linking markers characterized for CSCs and transcription factors involved in EMT. In the present review, studies of PIWI function are summarized, and the potential involvement of PIWI proteins in cancer development and progression is discussed. Contents1. Epigenetic alterations in cancer 2. P-element-induced wimpy testis (PIWI) proteins and PIWI-interacting RNAs (piRNAs) 3. PIWI-piRNA in cancer development 4. Characteristics of cancer stem cells (CSCs) 5. EMT in CSC development 6. Conclusions Epigenetic alterations in cancerCancer has been described as a set of diseases driven by progressive genetic abnormalities, including mutations in tumor suppressor genes, oncogenes and chromosomal abnormalities, and by aberrant epigenetic alterations (1). Epigenetic alterations identified in cancer include global DNA hypomethylation, particularly in repetitive regions, but also in the intronic and the coding regions of genes. These alterations may result in the reactivation of transposons, the loss of chromosomal stability and imprinting patterns. Another epigenetic modification is gene-specific DNA hypermethylation, particularly in promoter regions of tumor suppressor genes, deregulation of histone modification patterns and consequently alterations in gene expression. Additionally, small non-coding RNA (ncRNA) deregulation has been studied in detail in various types of cancer in recent years (1). All these alterations drive the transformation of wild-type cells into highly malignant tumor consisting of neoplastic cells with metastatic potential and unlimited proliferation capacities (1,2). P-element-induced wimpy testis (PIWI) proteins and PIWI-interacting RNAs (piRNAs)Currently, three major classes of small regulatory RNAs have been identified: microRNAs, small interfering...

show abstract

“…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 . Cheng et al reported that the expression of piR‐823 in gastric cancer tissues was significantly lower compared to non‐cancerous tissues and its increased expression inhibited growth of gastric cancer cells .…”

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

View full text Add to dashboard Cite

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.

show abstract

piR-651 promotes tumor formation in non-small cell lung carcinoma through the upregulation of cyclin D1 and CDK4

Cited by 74 publications

References 28 publications

PIWI-like protein, HIWI2 is aberrantly expressed in retinoblastoma cells and affects cell-cycle potentially through OTX2

PIWI-like protein, HIWI2 is aberrantly expressed in retinoblastoma cells and affects cell-cycle potentially through OTX2

The meaning of PIWI proteins in cancer development

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

Contact Info

Product

Resources

About