Abstract
Long non-coding (lnc)RNA ABHD11-AS1 participates in the development and progress of various cancers, but its role in colorectal cancer (CRC) remains poorly known. In the present study, public database analysis and quantitative reverse transcription PCR of CRC and normal tissues showed that ABHD11-AS1 was overexpressed in CRC and associated with poor prognosis in CRC patients. Both in vitro and in vivo experiments demonstrated that loss-of-function of ABHD11-AS1 attenuated the proliferation, migration, and invasion of CRC cells and induced their apoptosis. Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the phosphoinositide 3 kinase (PI3K)/Akt signaling pathway is a potential target of ABHD11-AS1. Additionally, we noted that ABHD11-AS1 deficiency reduced integrin subunit alpha (ITGA)5 expression, and impaired the phosphorylation of P85, focal adhesion kinase (FAK), and Akt1 in CRC cell lines and tumor tissues of nude mice. Furthermore, we observed that ITGA5 overexpression abrogated the effect of ABHD11-AS1 knockdown on the proliferation and invasion abilities of CRC cells. Taken together, our studies suggest that lncRNA ABHD11-AS1 promotes proliferation, migration, and invasion in CRC by activating the ITGA5/Fak/PI3K/Akt signaling pathway, and that the ITGA5/Fak/PI3K/Akt axis is a promising target for CRC therapy.
Highlights
Colorectal cancer (CRC) has the third highest incidence of malignant tumors and the fifth major cause of mortality in China [1]
We show that ABHD11-AS1 may function as an oncogene and that high ABHD11-AS1 expression is significantly correlated with poor prognosis in colorectal cancer (CRC) patients
ABHD11-AS1 was overexpressed in CRC tissues and indicated poor prognosis
Summary
Colorectal cancer (CRC) has the third highest incidence of malignant tumors and the fifth major cause of mortality in China [1]. Great progress has been made in its screening and treatment during the past decade, the prognosis for CRC patients is still poor and the 5-year overall survival rate is only 56.7% [2]. The limitations of screening strategies mean that patients are typically diagnosed with advanced disease, which is associated with an unfavorable clinical outcome. It is of great importance to identify a reliable and valid biomarker and molecular target for colorectal cancer. LncRNAs exceed 200 nucleotides in length and lack a protein coding ability. They are important regulators of biological processes, including chromosome structure modulation, epigenetic regulation, transcription, mRNA splicing, and translation [3, 4]. To date, only a few lncRNAs associated with CRC have been characterized in detail
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