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

Abstract

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.

Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene

“…Besides stem cell-specific expression in small intestine and colon, expression of ASCL2 has recently been documented in cancerous tissues of among others lung, stomach, and breast ( Wang et al., 2017 ). Although gene silencing has been reported for ASCL2 in a number of individual CRCs, potentially excluding such samples for STAR applications ( Jubb et al., 2006 ), it will be of great interest to verify whether ASCL2 also marks stem cell activity in tumorigenic lesions of other organs, as well as in their corresponding normal epithelia.…”

Bufalin inhibits gastric cancer invasion and metastasis by down-regulating Wnt/ASCL2 expression

“…Achaete-scute-like 2 (ASCL2), a transcription factor containing a basic helix-loop-helix (bHLH) domain, is a member of the achaete-scute complex-like (ASCL) gene family, which is also referred to as the ‘achaete-scute complex homolog’ family, ‘achaete-scute family basic helix-loop-helix transcription factor’, or mammalian achaete-scute homologs (MASH); there are five family members (ASCL1-ASCL5) [ 14 , 15 ]. ASCL2 is a master regulator of intestinal stem cell identity and a Wnt target gene.…”

Overexpression of the proneural transcription factor ASCL1 in chronic lymphocytic leukemia with a t(12;14)(q23.2;q32.3)

“…According to a meta-analysis of microarray data in the Oncomine database, ASCL1 was one of the top 1% overexpressed genes in acute adult T-cell leukemia/lymphoma (FC: 3.76, p = 3.43E-5) [ 24 , 42 , 43 ], while reduced expression of ASCL1 was reported in diffuse large B-cell, primary effusion and mantle cell lymphoma [ 24 , 43 ]. The biological consequences of the above observations are currently unknown.…”