Dataset Information

PIWI-interacting RNA-36712 restrains breast cancer progression and chemoresistance by interaction with SEPW1 pseudogene SEPW1P RNA.

ABSTRACT:

Background

Breast cancer is one of the most common malignancies and the major cause of cancer-related death in women. Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has been increasingly recognized, few studies have been explored the functional mechanism of piRNAs in breast cancer development and progression.

Methods

We examined the top 20 highly expressed piRNAs based on the analysis of TCGA breast cancer data in two patient cohorts to test the roles of piRNAs in breast cancer. The effects of piRNA-36,712 on the malignant phenotypes and chemosensitivity of breast cancer cells were detected in vitro and in vivo. MS2-RIP and reporter gene assays were conducted to identify the interaction and regulation among piRNA-36,712, miRNAs and SEPW1P. Kaplan-Meier estimate with log-rank test was used to compare patient survival by different piRNA-36,712 expression levels.

Results

We found piRNA-36,712 level was significantly lower in breast cancer than in normal breast tissues and low level was correlated with poor clinical outcome in patients. Functional studies demonstrated that piRNA-36,712 interacts with RNAs produced by SEPW1P, a retroprocessed pseudogene of SEPW1, and subsequently inhibits SEPW1 expression through competition of SEPW1 mRNA with SEPW1P RNA for microRNA-7 and microRNA-324. We also found that higher SEPW1 expression due to downregulation of piRNA-36,712 in breast cancer may suppress P53, leading to the upregulated Slug but decreased P21 and E-cadherin levels, thus promoting cancer cell proliferation, invasion and migration. Furthermore, we found that piRNA-36,712 had synergistic anticancer effects with the paclitaxel and doxorubicin, two chemotherapeutic agents for breast cancer.

Conclusions

These findings suggest that piRNA-36,712 is a novel tumor suppressor and may serve as a potential predictor for the prognosis of breast cancer patients.

SUBMITTER: Tan L

PROVIDER: S-EPMC6330501 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

PIWI-interacting RNA-36712 restrains breast cancer progression and chemoresistance by interaction with SEPW1 pseudogene SEPW1P RNA.

Tan Liping L Mai Dongmei D Zhang Bailin B Jiang Xiaobing X Zhang Jialiang J Bai Ruihong R Ye Ying Y Li Mei M Pan Ling L Su Jiachun J Zheng Yanfen Y Liu Zexian Z Zuo Zhixiang Z Zhao Qi Q Li Xiaoxing X Huang Xudong X Yang Jie J Tan Wen W Zheng Jian J Lin Dongxin D

Molecular cancer 20190112 1

<h4>Background</h4>Breast cancer is one of the most common malignancies and the major cause of cancer-related death in women. Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has been increasingly recognized, few studies have been explored the functional mechanism of piRNAs in breast cancer development and progression.<h4>Methods</h4>We examined the top 20 highly expressed piRNAs based on the analysis of TCGA breast cancer data in two patient cohorts to test the roles of piRNA ...[more]

PMID: 30636640

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Project description:PIWI-interacting RNAs (piRNAs) are a novel class of small ncRNAs initially isolated from germ line cells; although recent studies report that they are expressed also in somatic cells. To elucidate the role of piRNAs in somatic cells, in particular from breast cancer, we performed the first extensive next generation sequencing expression analysis of small RNA transcriptomes of hormone responsive breast cancer cell lines in different culture conditions. In addition, to understand the behavior of piRNAs with respect to miRNAs in breast tumor tissues, small RNA sequence data set available in Gene Expression Omnibus (GSE39162) database was used. Results led to the identification of ~100 and ~150 human piRNAs in the breast cancerous cell lines and tumors respectively, several of which differentially expressed in cell lines under different experimental conditions tested or in response to ERβ and in tumor tissues. Western blotting and Q-PCR analysis also revealed the presence in breast cell lines of PIWIL (PIWI Like) subfamily members proteins encoded in the human genome (PIWIL2/HILI and PIWIL4/HIWI2) and of other components of the piRNA biogenesis pathways, suggesting that this might indeed be functional in somatic cells. These results show that piRNAs are expressed in human somatic cells, in particular in cancer, where their expression is influenced by neoplastic transformation, growth conditions and estrogen receptor beta. More important, we demonstrate for the first time a distinct pattern of piRNAs expression in cancerous vs normal breast tissues, which suggests a potential role of these epigenetic modulators in mammary carcinogenesis and maintenance of the cancer cell phenotype. In addition, to understand the behavior of piRNAs with respect to miRNAs in breast tumor tissues, small RNA sequence data set available in Gene Expression Omnibus (GEO; GSM957192 TAX577740T ,GSM957194 TAX577740N, GSM957195 TAX577453T, GSM957197 TAX577453N, GSM957198 TAX577745T, GSM957200 TAX577745N, GSM957201 TAX577579T, GSM957203 TAX577579N) was used.

Dataset Information

PIWI-interacting RNA-36712 restrains breast cancer progression and chemoresistance by interaction with SEPW1 pseudogene SEPW1P RNA.

Background

Methods

Results

Conclusions

Publications

PIWI-interacting RNA-36712 restrains breast cancer progression and chemoresistance by interaction with SEPW1 pseudogene SEPW1P RNA.

Similar Datasets

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