Downregulation of long non-coding RNA MAFG-AS1 represses tumorigenesis of colorectal cancer cells through the microRNA-149-3p-dependent inhibition of HOXB8

Colorectal Cancer

Cancer Cell Int. 2020 Oct 19;20:511. doi: 10.1186/s12935-020-01485-4. eCollection 2020.


BACKGROUND: Colorectal cancer (CRC) is considered as the second common death-induced cancer. More recently, association of long non-coding RNAs (lncRNAs) with CRC has been extensively investigated. Therefore, the present study was performed to determine whether lncRNA MAF BZIP Transcription Factor G Antisense RNA 1 (MAFG-AS1) could regulate biological activities of CRC cells and unravel the underlying mechanisms.

METHODS: CRC and corresponding adjacent tissues were collected to determine the expression of lncRNA MAFG-AS1, microRNA-149-3p (miR-149-3p) and homeobox B8 (HOXB8) by RT-qPCR. Dual luciferase reporter gene assay was used to explore the targeting relationship between miR-149-3p and lncRNA MAFG-AS1 and between miR-149-3p and HOXB8, followed by RNA immunoprecipitation for verification. Migration, proliferation, invasion, and apoptosis of HCT116 and LoVo cells were examined when lncRNA MAFG-AS1 was silenced or miR-149-3p was overexpressed. Furthermore, tumorigenicity of HCT116 and LoVo cells was measured in vivo by tumor xenograft in nude mice.

RESULTS: LncRNA MAFG-AS1 and HOXB8 were found to be highly expressed in CRC tissues and cells, while miR-149-3p was under-expressed. LncRNA MAFG-AS1 negatively regulated miR-149-3p while miR-149-3p downregulated HOXB8. In addition, lncRNA MAFG-AS1 silencing by shRNA or miR-149-3p upregulation by mimic suppressed the migration, proliferation, invasion and tumorigenesis but promoted the apoptosis of HCT116 and LoVo cells.

CONCLUSION: Taken together, lncRNA MAFG-AS1 downregulation inhibits the malignant behaviors of CRC cells by upregulating miR-149-3p and downregulating HOXB8, providing a potential therapeutic target for CRC treatment.