Abstract

Long non-coding RNAs (lncRNAs) are involved in the development of many cancers, including colorectal cancer (CRC). FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) is a key lncRNA in the regulation of CRC progression, but its potential molecular mechanisms need to be further explored. To investigate the mechanism of lncRNA FEZF1-AS1 in the progression of CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure FEZF1-AS1 and miR-363-3p expression. Cell proliferation, migration and invasion were analyzed using Cell Counting Kit-8 (CCK-8) and transwell assays. Protein expression of epithelial-mesenchymal transformation (EMT)-related markers and paired-related homeobox 1 (PRRX1) were determined using western blot analysis. The interactions among FEZF1-AS1, miR-363-3p and PRRX1 were verified with dual-luciferase reporter assay. A xenograft model was constructed in vivo to confirm the role of FEZF1-AS1 in CRC tumor growth. We demonstrated that FEZF1-AS1 expression was upregulated in CRC, and its silencing reduced CRC cell proliferation, migration, invasion, and EMT. MiR-363-3p could be inhibited by FEZF1-AS1, which inhibitor could reverse the suppressive effect of FEZF1-AS1 silencing on CRC progression. Paired-related homeobox 1 could be targeted by miR-363-3p, and the inhibitory effect of FEZF1-AS1 knockdown on CRC progression could also be eliminated by PRRX1 overexpression. Furthermore, interference of FEZF1-AS1 reduced the tumor growth of CRC in vivo. Our data demonstrate that FEZF1-AS1 regulated PRRX1 expression to promote CRC progression via inhibition of miR-363-3p.

Highlights

  • Long non-coding RNAs are involved in the development of many cancers, including colorectal cancer (CRC)

  • We demonstrated that FEZF1-AS1 expression was upregulated in CRC, and its silencing reduced CRC cell proliferation, migration, invasion, and epithelial–mesenchymal transformation (EMT)

  • Paired-related homeobox 1 could be targeted by miR-363-3p, and the inhibitory effect of FEZF1-AS1 knockdown on CRC progression could be eliminated by paired-related homeobox 1 (PRRX1) overexpression

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Summary

Introduction

Long non-coding RNAs (lncRNAs) are involved in the development of many cancers, including colorectal cancer (CRC). FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) is a key lncRNA in the regulation of CRC progression, but its potential molecular mechanisms need to be further explored. Colorectal cancer (CRC) is one of the most common malignant tumors, with more than 1.2 million new CRC patients diagnosed annually.[1,2] The age of CRC patient tends to be older (41–65 years), and is more common in females.[3] At present, the leading cause of death in CRC patients was tumor metastasis,[4] a process driven by epithelial–mesenchymal transformation (EMT).[5] it is urgent to explore the mechanism affecting CRC metastasis. Increasing evidence reveals that long non-coding RNAs (lncRNAs) are involved in the regulation of cancer progression, including CRC.[6,7] The lncRNA is a kind of non-protein coding RNA with a length of more than 200 nucleotides (nts),[8] and mainly participates in the regulation of gene expression as a competitive endogenous RNA (ceRNA) that adsorbs microRNAs (miRNAs).[9,10] Studies have shown that a variety of lncRNAs (such as NKILA, BLACAT2 and MEG3) are abnormally expressed in CRC, which can modulate its occurrence and development.[11,12,13]

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