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LncRNA MANCR Acts as a ceRNA to Sponge MicroRNA-20a-5p and Upregulate GCNT4 to Suppress Angiogenesis in Colorectal

Wei Zheng¹, ShuRong Huang¹, YangQiang Wang¹

¹Department of Gastrointestinal Surgery, Quanzhou First Hospital, Quanzhou, Fujian, 362000, China.

Critical Reviews in Eukaryotic Gene Expression

|March 13, 2026

Abstract

Background:

Colorectal cancer (CRC) is ranked among the most prevalent digestive system malignancies worldwide. Its progression is closely associated with angiogenesis, which not only supplies nutrients and oxygen to tumors but also facilitates metastasis. Dysregulation of lncRNA MANCR (MANCR) in multiple cancers influences tumorigenesis and development. However, the function and molecular mechanism of MANCR in CRC angiogenesis remain unclear.

Methods:

This study constructed a MANCR/miR-20a-5p/GCNT4 axis using TCGA, starBase, and TargetScan Human databases. Expression of MANCR, microRNA-20a-5p, and GCNT4 in CRC was analyzed using the TCGA database, with validation performed in cell lines. In vitro functional assays (CCK-8, colony formation, transwell migration/invasion, tube formation, and Western blotting) were conducted to evaluate the impact of MANCR on CRC cell proliferation, migration, invasion, and angiogenesis. Bioinformatics analysis was used to analyze the Pearson correlation between MANCR and microRNA-20a-5p, and between microRNA-20a-5p and GCNT4. Functional interactions of MANCR and microRNA-20a-5p, and ceRNA regulatory mechanisms were verified via dual-luciferase reporter assays, RNA pull-down, and RNA immunoprecipitation, with further exploration of GCNT4's role in angiogenesis regulation conducted.

Results:

Significant downregulation of MANCR expression was observed in CRC tissues and cell lines. Overexpression of MANCR robustly inhibited CRC cell proliferation, migration, invasion, and angiogenesis. Significant negative correlations were observed between MANCR and microRNA-20a-5p, and between microRNA-20a-5p and GCNT4. MANCR sponged microRNA-20a-5p to downregulate its expression, while microRNA-20a-5p repressed GCNT4 expression by binding to the 3'UTR of GCNT4 mRNA. Overexpression of microRNA-20a-5p reversed MANCR-mediated suppression of angiogenesis.

Conclusion:

LncRNA MANCR sponges microRNA-20a-5p, relieves the suppression of GCNT4 expression caused by microRNA-20a-5p, and elevates GCNT4 expression, ultimately inhibiting tumor growth and angiogenesis in CRC.

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lncRNA - Long Non-coding RNAs

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...

lncRNA - Long Non-coding RNAs

lncRNA - Long Non-coding RNAs

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...

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RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
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