MicroRNA-200 (miR-200) Cluster Regulation by Achaete Scute-like 2 (Ascl2)

Yin, Tian; Pan, Qiong; Shang, Yangyang; Zhu, Rong; Ye, Jun; Liu, Yun; Zhong, Xiaoli; Li, Shanshan; He, Yonghong; Chen, Lei; Zhao, Jingjing; Chen, Wensheng; Peng, Zhihong; Wang, Rongquan

doi:10.1074/jbc.m114.598383

Cited by 85 publications

(55 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…16 A direct link between miRs and EMT was firmly established and specifically the miR-200 family has been implicated in repressing the EMT-inducing zinc-finger E-box binding homeobox transcription factors ZEB1 and ZEB2, 17, 18 thereby inhibiting the EMT program. Also in CRC miR-200 family members have been shown to regulate the transition between distinct cellular states, 19 and to play a role in development of metastatic disease. Cells at the invasive front of tumors downregulate miR-200 expression, allowing them to undergo EMT and leave the primary tumor.…”

Section: Introductionmentioning

confidence: 99%

A multidimensional network approach reveals microRNAs as determinants of the mesenchymal colorectal cancer subtype

et al. 2016

View full text Add to dashboard Cite

Colorectal cancer (CRC) is a heterogeneous disease posing a challenge for accurate classification and treatment of this malignancy. There is no common genetic molecular feature that would allow for the identification of patients at risk for developing recurrences and thus selecting patients who would benefit from more stringent therapies still poses a major clinical challenge. Recently, an international multicenter consortium (CRC Subtyping Consortium) was established aiming at the classification of CRC patients in biologically homogeneous CRC subtypes. Four consensus molecular subtypes (CMSs) were identified, of which the mesenchymal CMS4 presented with worse prognosis signifying the importance of identifying these patients. Despite the large number of samples analyzed and their clear association with unifying biological programs and clinical features, single-driver mutations could not be identified and patients are heterogeneous with regard to currently used clinical markers. We therefore set out to define the regulatory mechanisms underlying the distinct gene expression profiles using a network-based approach involving multiple molecular modalities such as gene expression, methylation levels and microRNA (miR) expression. The miR-200 family presented as the most powerful determinant of CMS4-specific gene expression, tuning the majority of genes differentially expressed in the poor prognosis subtype, including genes associated with the epithelial–mesenchymal transition program. Furthermore, our data show that two epigenetic marks, namely the methylation of the two miR-200 promoter regions, can identify tumors belonging to the mesenchymal subtype and is predictive of disease-free survival in CRC patients. Importantly, epigenetic silencing of the miR-200 family is also detected in epithelial CRC cell lines that belong to the mesenchymal CMS. We thus show that determining regulatory networks is a powerful strategy to define drivers of distinct cancer subtypes, which possess the ability to identify subtype affiliation and to shed light on biological behavior.

show abstract

Section: Introductionmentioning

confidence: 99%

A multidimensional network approach reveals microRNAs as determinants of the mesenchymal colorectal cancer subtype

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The ASCL2 may form a complex with the Wnt pathway signal transducer β-catenin in order to synergistically activate the expression of downstream target genes (11,12). Moreover, ASCL2 may modulate the plasticity between epithelial and mesenchymal characteristics in colon cancer (13). …”

Section: Introductionmentioning

confidence: 99%

Systematic analysis of the achaete-scute complex-like gene signature in clinical cancer patients

Wang

Shahi

Huang

et al. 2016

Molecular and Clinical Oncology

View full text Add to dashboard Cite

The achaete-scute complex-like (ASCL) family, also referred to as ‘achaete-scute complex homolog’ or ‘achaete-scute family basic helix-loop-helix transcription factor’, is critical for proper development of the nervous system and deregulation of ASCL plays a key role in psychiatric and neurological disorders. The ASCL family consists of five members, namely ASCL1, ASCL2, ASCL3, ASCL4 and ASCL5. The ASCL1 gene serves as a potential oncogene during lung cancer development. There is a correlation between increased ASCL2 expression and colon cancer development. Inhibition of ASCL2 reduced cellular proliferation and tumor growth in xenograft tumor experiments. Although previous studies demonstrated involvement of ASCL1 and ASCL2 in tumor development, little is known on the remaining ASCL family members and their potential effect on tumorigenesis. Therefore, a holistic approach to investigating the expression of ASCL family genes in diverse types of cancer may provide new insights in cancer research. In this study, we utilized a web-based microarray database (Oncomine; ) to analyze the transcriptional expression of the ASCL family in clinical cancer and normal tissues. Our bioinformatics analysis revealed the potential involvement of multiple ASCL family members during tumor onset and progression in multiple types of cancer. Compared to normal tissue, ASCL1 exhibited a higher expression in cancers of the lung, pancreas, kidney, esophagus and head and neck, whereas ASCL2 exhibited a high expression in cancers of the breast, colon, stomach, lung, head and neck, ovary and testis. ASCL3, however, exhibited a high expression only in breast cancer. Interestingly, ASCL1 expression was downregulated in melanoma and in cancers of the bladder, breast, stomach and colon. ASCL2 exhibited low expression levels in sarcoma, melanoma, brain and prostate cancers. Reduction in the expression of ASCL3 was detected in lymphoma, bladder, cervical, kidney and epithelial cancers. Similarly, ASCL5 exhibited low expression in the majority of brain cancer subtypes, such as glioblastoma and oligodendroglioma. This analysis supports the hypothesis that specific ASCL members may play an important role in cancer development. Collectively, our data suggest that alterations in the expression of ASCL gene family members are correlated with cancer development. Furthermore, ASCL family members were categorized according to cancer subtype. The aim of this report was to provide novel insights to the significance of the ASCL family in various cancers and our findings suggested that the ASCL gene family may be an ideal target for future cancer studies.

show abstract

“…For example, miR-216b and miR-486-5p inhibit invasion and metastasis of liver cancer cells[45, 46], while miR-421 can promote metastasis of gastric cancer and neuroblastoma[47]. In the transcription regulation networks of crosstalk modules, miR-1[48], miR-128[49], miR-1297 [50], and miR-429[51] all have inhibitory functions on the metastasis of CRC, which further validates the accuracy of our prediction. Furthermore, some of other miRNAs we identified are also closely associated with metastasis of other tumor types.…”

Section: Resultsmentioning

confidence: 99%

A multidimensional integration analysis reveals potential bridging targets in the process of colorectal cancer liver metastasis

et al. 2017

View full text Add to dashboard Cite

Approximately 9% of cancer-related deaths are caused by colorectal cancer. Liver metastasis is a major factor for the high colorectal cancer mortality rate. However, the molecular mechanism underlying colorectal cancer liver metastasis remains unclear. Using a global and multidimensional integration approach, we studied sequencing data, protein-protein interactions, and regulation of transcription factor and non-coding RNAs in primary tumor samples and liver metastasis samples to unveil the potential bridging molecules and the regulators that functionally link different stages of colorectal cancer liver metastasis. Primary tumor samples and liver metastasis samples had modules with significant overlap and crosstalk from which we identified several bridging genes (e.g. KNG1 and COX5B), transcription factors (e.g. E2F4 and CDX2), microRNAs (e.g. miR-590-3p and miR-203) and lncRNAs (e.g. lincIRX5 and lincFOXF1) that may play an important role in the process of colorectal cancer liver metastasis. This study enhances our understanding of the genetic alterations and transcriptional regulation that drive the metastatic process, but also provides the methodology to guide the studies on other metastatic cancers.

show abstract

MicroRNA-200 (miR-200) Cluster Regulation by Achaete Scute-like 2 (Ascl2)

Cited by 85 publications

References 33 publications

A multidimensional network approach reveals microRNAs as determinants of the mesenchymal colorectal cancer subtype

A multidimensional network approach reveals microRNAs as determinants of the mesenchymal colorectal cancer subtype

Systematic analysis of the achaete-scute complex-like gene signature in clinical cancer patients

A multidimensional integration analysis reveals potential bridging targets in the process of colorectal cancer liver metastasis

Contact Info

Product

Resources

About