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http://purl.uniprot.org/citations/33831429http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33831429http://www.w3.org/2000/01/rdf-schema#comment"

Background

Recent studies have provided compelling evidence regarding the association of microRNAs (miRNAs) with the progression and development of tumors. Among the miRNAs, the dysregulation of miR-146b-3p expression has been reported in several cancers, however, its effect on colorectal cancer (CRC) remains unexplored. Many studies have suggested a close correlation between the transcription factor (TF)-miRNA signal and cancer. The present study explored the effects of TF-miR-146b-3p axis on CRC and elucidated its downstream regulatory molecule.

Materials and methods

The expression levels of miR-146b-3p in CRC tissues and cell lines were assessed via quantitative real-time polymerase chain reaction (qRT-PCR). The impact of miR-146b-3p on CRC cell proliferation, migration, and invasion were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell proliferation assay and transwell migration and invasion assay. Additionally, the impact of miR-146b-3p on CRC cell cycle and apoptosis was investigated using flow cytometry. The targets of miR-146b-3p, predicted by miRWalk database, were verified using a dual-luciferase reporter system. The expression levels of TFs were detected using qRT-PCR. The effects of miR-146b-3p and SP1 on FAM107A expression were assessed by performing qRT-PCR and western blotting. Chromatin Immunoprecipitation (ChIP) Assay was performed and JASPAR database was utilized to explore the regulatory relationship between the SP1 and miR-146b-3p.

Results

Increased expression of miR-146b-3p in CRC tissues and cell lines correlated with poor overall survival (OS). Upregulation of miR-146b-3p expression remarkably promoted the proliferation, migration, and invasion of CRC cells and suppressed their apoptosis. Furthermore, SP1 overexpression significantly elevated the miR-146b-3p expression, decreased the FAM107A expression, and promoted the G1/S transition. The miR-146b-3p overexpression also enhanced the effects of SP1 overexpression on CRC cell proliferation, migration, and invasion, whereas miR-146b-3p knockdown led to the opposite results.

Conclusion

Mechanistically, miR-146b-3p functions as an oncogene by directly targeting FAM107A. Our results highlight the critical regulatory role played by SP1-induced miR-146b-3p expression in CRC development. Our results suggest that SP1/miR-146b-3p/FAM107A axis may be a potential therapeutic target for CRC."xsd:string
http://purl.uniprot.org/citations/33831429http://purl.org/dc/terms/identifier"doi:10.1016/j.lfs.2021.119398"xsd:string
http://purl.uniprot.org/citations/33831429http://purl.uniprot.org/core/author"Ma X."xsd:string
http://purl.uniprot.org/citations/33831429http://purl.uniprot.org/core/author"Wang D."xsd:string
http://purl.uniprot.org/citations/33831429http://purl.uniprot.org/core/author"Wang G."xsd:string
http://purl.uniprot.org/citations/33831429http://purl.uniprot.org/core/author"Tao K."xsd:string
http://purl.uniprot.org/citations/33831429http://purl.uniprot.org/core/author"Feng M."xsd:string
http://purl.uniprot.org/citations/33831429http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33831429http://purl.uniprot.org/core/name"Life Sci"xsd:string
http://purl.uniprot.org/citations/33831429http://purl.uniprot.org/core/pages"119398"xsd:string
http://purl.uniprot.org/citations/33831429http://purl.uniprot.org/core/title"Transcription factor SP1-induced microRNA-146b-3p facilitates the progression and metastasis of colorectal cancer via regulating FAM107A."xsd:string
http://purl.uniprot.org/citations/33831429http://purl.uniprot.org/core/volume"277"xsd:string
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