The p300/YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer

Tang, Weimei; Zhou, Weijie; Li, Xiang; Wu, Xiaosheng; Zhang, Pei; Wang, Jing; Liu, Guangnan; Zhang, Wenjing; Peng, Ying; Huang, Xiaoting; Cai, Jianqun; Bai, Yang; Bai, Lan; Zhu, Wei; Gu, Huijie; Xiong, Jing; Chen, Ye; Li, Aimin; Liu, Side; Wang, Jide

doi:10.1038/s41467-018-08225-3

Cited by 106 publications

(86 citation statements)

References 42 publications

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“…The transcription factor YY1 is associated with cell differentiation, apoptosis and tumorigenesis [54]. The abnormal expression of YY1 contributes to several human cancers and correlates with poor prognosis [55,56]. However, the function of YY1 in breast cancer remains controversial [57][58][59].…”

Section: Discussionmentioning

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

132

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: Discussionmentioning

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

132

103

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“…8,9 Identification of their direct targets has led to deciphering their functional effects and their promise as therapeutic targets. 10,11 Here, we sequenced the miRNome of a long-term follow-up thyroid cancer series enriched with poor prognosis cases and found hsa-miR139-5p downregulation as a bona fide poor-prognostic factor. Exogenous hsa-miR-139-5p expression repressed procancer features of thyroid cancer (TC) cells.…”

Section: Introductionmentioning

confidence: 97%

“…MiRNome profiling has uncovered markers associated with specific clinicopathological features for many cancer types, including thyroid cancer . Identification of their direct targets has led to deciphering their functional effects and their promise as therapeutic targets …”

Section: Introductionmentioning

confidence: 99%

Hsa‐miR‐139‐5p is a prognostic thyroid cancer marker involved in HNRNPF‐mediated alternative splicing

Montero‐Conde

Graña‐Castro

Martín-Serrano

et al. 2019

Intl Journal of Cancer

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It is critical to identify biomarkers and functional networks associated with aggressive thyroid cancer to anticipate disease progression and facilitate personalized patient management. We performed miRNome sequencing of 46 thyroid tumors enriched with advanced disease patients with a median follow‐up of 96 months. MiRNome profiles correlated with tumor‐specific histopathological and molecular features, such as stromal cell infiltration and tumor driver mutation. Differential expression analysis revealed a consistent hsa‐miR‐139‐5p downexpression in primary carcinomas from patients with recurrent/metastatic disease compared to disease‐free patients, sustained in paired local metastases and validated in publicly available thyroid cancer series. Exogenous expression of hsa‐miR‐139‐5p significantly reduced migration and proliferation of anaplastic thyroid cancer cells. Proteomic analysis indicated RICTOR, SMAD2/3 and HNRNPF as putative hsa‐miR‐139‐5p targets in our cell system. Abundance of HNRNPF mRNA, encoding an alternative splicing factor involved in cryptic exon inclusion/exclusion, inversely correlated with hsa‐miR‐139‐5p expression in human tumors. RNA sequencing analysis revealed 174 splicing events differentially regulated upon HNRNPF repression in our cell system, affecting genes involved in RTK/RAS/MAPK and PI3K/AKT/MTOR signaling cascades among others. These results point at the hsa‐miR‐139‐5p/HNRNPF axis as a novel regulatory mechanism associated with the modulation of major thyroid cancer signaling pathways and tumor virulence.

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“…In our study, we discovered that YY1, which can regulate many lncRNAs as a transcription factor, was poorly expressed in GC with the potential of inhibiting SNHG12 transcription. We cannot exclude other mechanisms behind the transcriptional suppression of SNHG12 by YY1, as YY1 can bind to HDAC which inhibits histone acetylation (25), we speculate that YY1 may suppress the transcription of SNHG12 via direct binding to SNHG12 promotor region and inducing epigenetic modi cation. However, this hypothesis requires more veri cation and the detailed mechanisms of the transcriptional suppression of SNHG12 by YY1 remain to be discovered in the future.…”

Section: Discussionmentioning

confidence: 94%

YY1-modulated Long Non-coding RNA SNHG12 Predicts and Promotes Gastric Cancer Metastasis via Activating miR-218-5p/YWHAZ-dependent β-catenin: A Bed to Bench Approach

Zhang¹,

Dai²,

Beeharry³

et al. 2020

Preprint

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Background: Gastric Cancer (GC) is one of the leading causes of cancer-related deaths and mortality. Long non-coding RNAs (lncRNAs) such as SNHG12 play important roles in the pathogenesis and progression of cancers. However, the role and significanve of SNHG12 in the metastasis of GC has not yet been thoroughly investigated.Methods: The SNHG12 expression pattern was detected in GC tissue samples from our faculty and cell lines using quantitative reverse transcription PCR. In vivo and in vitro gain and loss assays were conducted to observe the effects of SNHG12 regulation on GC cell metastasis potential. The underlying mechanisms of SNHG12 regulation on EMT and metastatic potential of GC cells were further determined by quantitative reverse transcription PCR, western blotting, dual luciferase reporter assays, co-immunoprecipitation, immunoprecipitation, RIP assays, TOPFlash/FOPFlash reporter assays and Ch-IP assays.Results: SNHG12 was upregulated in GC tissues and cell lines. The expression levels of SNHG12 in GC samples was significantly related to tumor invasion depth, TNM staging and lymph node metastasis, and was associated with poorer DFS and OS in the GC patients. SNHG12 was significantly highly expressed in peritoneal metastatic tissues from GC patients and mice subjects, suggesting a possible role of SNHG12 in peritoneal carcinomatosis from GC. Further in vivo and in vitro gain and loss assays indicated that SNHG12 promoted GC metastasis and EMT. Based on hypothetical bioinformatic analysis findings, our mechanistic analyses revealed that miR-218-5p was a direct target of SNHG12 and suggested that both SNHG12 and miR-218-5p could collectively regulate YWHAZ, forming the SNHG12/ miR-218-5p/YWHAZ axis, hereby decreasing the ubiquitination of β-catenin, thus activating the β-catenin signaling pathway and facilitating metastasis and EMT. Further analysis also revealed that the transcription factor YY1 could negatively modulate SNHG12 transcription.Conclusions: Our findings demonstrate that SNHG12 is be a potential prognostic marker and therapeutic target for GC. Negatively modulated by transcription factor YYI, SNHG12 promotes GC metastasis and EMT by regulating the miR-218-5p/YWHAZ axis and hence activating the β-catenin signaling pathway. Furthermore, we discovered high SNHG12 expression could be related to peritoneal carcinomatosis from GC but this requires further validation.

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The p300/YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer

Cited by 106 publications

References 42 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

Hsa‐miR‐139‐5p is a prognostic thyroid cancer marker involved in HNRNPF‐mediated alternative splicing

YY1-modulated Long Non-coding RNA SNHG12 Predicts and Promotes Gastric Cancer Metastasis via Activating miR-218-5p/YWHAZ-dependent β-catenin: A Bed to Bench Approach

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