LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling

Luo, Jie; Wang, Keliang; Yeh, Shuyuan; Sun, Yin; Liang, Liang; Xiao, Yao; Xu, Wanhai; Niu, Yuanjie; Cheng, Liang; Maity, Sankar N.; Jiang, Runze; Chang, Chawnshang

doi:10.1038/s41467-019-09784-9

Cited by 158 publications

(104 citation statements)

References 57 publications

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“…Recent findings indicate that lncRNAs can exert their function in different compartments of the cell. Most of the lncRNAs that have been investigated thus far act in the nucleus by regulating gene expression [40]. However, lncRNAs also act as ceRNAs to regulate mRNA degradation and translation in the cytoplasm [41].…”

Section: Linc00673 Regulates Mark4 Expression By Competing For Mir-51mentioning

confidence: 99%

LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

Qiao

Ning

Wan

et al. 2019

J Exp Clin Cancer Res

141

103

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Background An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play essential roles in tumor initiation and progression. LncRNAs act as tumor promoters or suppressors by targeting specific genes via epigenetic modifications and competing endogenous RNA (ceRNA) mechanisms. In this study, we explored the function and detailed mechanisms of long intergenic nonprotein coding RNA 673 (LINC00673) in breast cancer progression. Methods Quantitative real-time PCR (qRT-PCR) was used to examine the expression of LINC00673 in breast cancer tissues and in adjacent normal tissues. Gain-of-function and loss-of function experiments were conducted to investigate the biological functions of LINC00673 in vitro and in vivo. We also explored the potential role of LINC00673 as a therapeutic target using antisense oligonucleotide (ASO) in vivo. RNA sequencing (RNA-seq), dual-luciferase reporter assays, chromatin immunoprecipitation (ChIP) assay, and rescue experiments were performed to uncover the detailed mechanism of LINC00673 in promoting breast cancer progression. Results In the present study, LINC00673 displayed a trend of remarkably increased expression in breast cancer tissues and was associated with poor prognosis in breast cancer patients. Importantly, LINC00673 depletion inhibited breast cancer cell proliferation by inhibiting the cell cycle and increasing apoptosis. Furthermore, ASO therapy targeting LINC00673 substantially suppressed breast cancer cell proliferation in vivo. Mechanistically, LINC00673 was found to act as a ceRNA by sponging miR-515-5p to regulate MARK4 expression, thus inhibiting the Hippo signaling pathway. Finally, ChIP assay showed that the transcription factor Yin Yang 1 (YY1) could bind to the LINC00673 promoter and increase its transcription in cis. Conclusions YY1-activated LINC00673 may exert an oncogenic function by acting as a sponge for miR-515-5p to upregulate the MARK4 and then inhibit Hippo signaling pathway, and may serve as a potential therapeutic target.

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Section: Linc00673 Regulates Mark4 Expression By Competing For Mir-51mentioning

confidence: 99%

LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

Qiao

Ning

Wan

et al. 2019

J Exp Clin Cancer Res

141

103

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“…Enhancer of Zeste 2 (EZH2) is a gene that is highly conserved as well as expressed in multiple human cancers [27]. EZH2 is aberrantly expressed in glioma and has strong effects on PCa proliferation and metastasis [28][29][30]. Studies show that EZH2 functions in the maintenance of cancer stem-like cell (CSC) properties [31].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of circ-TRPS1 suppressed prostatic cancer prognoses by regulating miR-124-3p/EZH2 axis-mediated stemness

Sha

Lei

Han

et al. 2020

Preprint

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Background: Abnormal circular RNA (circRNA) expression correlates with human traits such as many kinds of cancers. Though circRNAs have links to cancer, they have less characterization in metastatic castration-resistant prostate cancer (PCa), which is main reason for PCa mortality.Methods: Therefore, high-throughput sequencing was used for selected circRNA profiles. We performed RT-qPCR to determine circ-TRPS1 expression regarding PCa tissues. We used fluorescence in situ hybridization (FISH) to detect circ-TRPS1 expression and circ-TRPS1 subcellular localization in PCa tissues. circ-TRPS1 expression in PCa cells was selectively regulated. We employed CCK8, transwell assays to monitor the cell proliferation and invasion, respectively. We employed dual-luciferase reporter and RNA pulldown assays to verify the relationship among circ-TRPS1, miR-124-3p, and EZH2. We examined the circ-TRPS1 effects on PCa cell metastasis and proliferation in vivo through a subcutaneous xenograft model as well as an intravenous tail injection model of nude mice.Results: The result showed that circ-TRPS1 was upregulated significantly in high-grade PCa tissues or cell lines. High circ-TRPS1 expression correlated to aggressive PCa phenotypes. Knockdown of circ-TRPS1 suppressed PCa proliferation and metastasis through targeting miR-124-3p/EZH2 axis-mediated stemness in PCa, which was validated by luciferase reporter assays. EZH2 overexpression or miR-124-3p inhibition reversed the inhibition of circ-TRPS1 silencing in PCa cell migration and proliferation by recovering stemness.Conclusion: In summary, data demonstrated that circ-TRPS1 suppressed PCa progression through functioning similar to a miR-124-3p sponge to enhance EZH2 expression and cancer stem-like cell differentiation. Thus, circ-TRPS1 might be a candidate target for PCa treatment.

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“…LncRNAs suppress (Rinn et al, 2007;Kaneko et al, 2014;Kim et al, 2018) or activate (Wang et al, 2011;Gomez et al, 2013;Luo et al, 2019; gene transcription by binding to chromatin remodeling protein complexes and by acting as transcriptional enhancers (Lai et al, 2013;Jiang et al, 2018). In addition, lncRNAs post-transcriptionally regulate mRNAs, such as pre-mRNA alternative splicing (Beltran et al, 2008;Andersen et al, 2019), mRNA stability (Yang et al, 2014;Liu et al, 2014), and translation into proteins (Yoon et al, 2012;Malakar et al, 2019;Liu et al, 2019).…”

Section: Introduction Long Noncoding Rnasmentioning

confidence: 99%

The Oncogenic and Tumor Suppressive Functions of the Long Noncoding RNA MALAT1: An Emerging Controversy

2020

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Long noncoding RNAs are recently emerging as critical factors of tumorigenesis. Originally regarded as a pre-messenger RNA (mRNA) splicing regulator, the long noncoding RNA MALAT1 has been demonstrated to regulate gene transcription by binding histone modification enzymes and transcription factors, and to regulate mRNA and protein expression post-transcriptionally by binding microRNAs (miRNAs) and acting as a sponge. Early studies consistently report that MALAT1 is up-regulated in human cancer tissues of various organ origins, particularly metastatic cancer tissues, that high levels of MALAT1 expression in cancer tissues are associated with poor patient prognosis, and that MALAT1 induces cancer cell proliferation, migration, and invasion in vitro and tumor metastasis in mice. By contrast, by analyzing multiple independent large datasets, MALAT1 have very recently been found to be down-regulated in human colorectal and breast cancer tissues, and low MALAT1 expression is associated with decreased patient survival. By binding to the transcription factor TEAD, MALAT1 suppresses metastasis gene expression, colorectal and breast cancer cell migration, invasion, and metastasis in vitro and in mice. MALAT1 has therefore been proposed to function as a tumor suppressor in colorectal and breast cancers. More comprehensive studies with multiple independent cohorts of human cancer tissues of various organ origins, in vitro and in vivo function, and mechanism studies with rescue experiments are required to confirm the oncogenic or tumor suppressive role of MALAT1 in other cancers.

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LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling

Cited by 158 publications

References 57 publications

LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

Downregulation of circ-TRPS1 suppressed prostatic cancer prognoses by regulating miR-124-3p/EZH2 axis-mediated stemness

The Oncogenic and Tumor Suppressive Functions of the Long Noncoding RNA MALAT1: An Emerging Controversy

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