The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer

Abstract

Abnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

Establishment of quantitative nested-PCR of Abelson interactor 1 transcript variant-11

“…According to our previous study, the ABI1-TSV-11 variant in the SW480-ABI1-TSV-11 cell line was overexpressed compared with the SW480 and SW480-EV cell lines, as confirmed by Western blot analysis [ 6 ]. In this study, we developed the new strategy of detecting the mRNA level of the ABI1-TSV-11 variant by quantitative Nested-PCR.…”

“…To explore the specificity of nested PCR, we performed a nested-PCR assay using ABI1-TSV-11-overexpressed cell lines. The stable SW480 and LoVo cell lines were described in our previous study [ 6 ]. We performed the pre-amplification regular PCR run at 20 cycles, 25 cycles and 30 cycles.…”

“…Recent studies have shown that ABI1 is highly expressed in CRC tissues [ 7 ]. In addition to abnormal expression, different transcriptional variants (TSVs) of ABI1 may perform distinct biological functions [ 8 ]and play an important role in the progress of CRC metastasis [ 6 , 9 ]. There are eighteen TSVs generated from ABI1 primary transcript by alternative splicing ( https://www.ncbi.nlm.nih.gov/gene/10006 ).…”

“…There are eighteen TSVs generated from ABI1 primary transcript by alternative splicing ( https://www.ncbi.nlm.nih.gov/gene/10006 ). In our previous studies, we demonstrated that ABI1-TSV-11 is involved in the metastasis and poor prognosis of left-sided colorectal cancer (LsCC), and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) [ 6 ]. In addition, based on the analysis results of clinical follow-up information from The Cancer Genome Atlas (TCGA) [ 10 ] and RNA-seq data from TSVdb ( http://tsvdb.com ) [ 11 ], ABI1-TSV-11 could be used as an independent biomarker to evaluate the prognosis of LsCC.…”

“…Metastasis is a dynamic biological process that includes separation from the primary site, degradation of extracellular matrix, invasion into blood and lymphatic vessels, migration and movement in vessels, and distant colonization and neovascularization [ 2 , 3 ]. CRC metastasis is the leading cause of death, and Abelson interactor 1 (ABI1) is an important adaptor protein and its abnormal expression plays an important role in regulating the behaviors of tumor cells, such as proliferation, adhesion, migration and invasion, and thereby affecting the metastasis and progression of CRC [ 4 , 5 , 6 ]. Recent studies have shown that ABI1 is highly expressed in CRC tissues [ 7 ].…”