Downregulation of long non-coding RNA MAFG-AS1 represses tumorigenesis of colorectal cancer cells through the microRNA-1
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PRIMARY RESEARCH
Cancer Cell International Open Access
Downregulation of long non‑coding RNA MAFG‑AS1 represses tumorigenesis of colorectal cancer cells through the microRNA‑149‑3p‑dependent inhibition of HOXB8 Zhiyan Ruan1†, Hongling Deng1†, Minhua Liang1, Zhe Xu1, Manxiang Lai1, Hong Ren1, Xiangliang Deng2* and Xinguo Su1*
Abstract 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 MAFGAS1, 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 miR149-3p 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. Keyword: Long non-coding RNA MAFG-AS1, microRNA-149-3p, homeobox B8, colorectal cancer, biological characteristics *Correspondence: [email protected]; [email protected] † Zhiyan Ruan and Hongling Deng contributed equally to this work. 1 School of Pharmacy, Guangdong Province, Guangdong Food & Drug Vocational College, No. 321, Longdong North Road, Tianhe District, Guangzhou 510520, P.R. China 2 School of Chinese Medicine, Guangdong Pharmaceutical University, No. 280, East Ring Road, Guangzhou University Town, Guangzhou 510006, P.R. China
Background Colorectal cancer (CRC) is regarded as the third most common malignant cancers and the second leading cause of cancer-related death across the world, resulting in approximately 881,000 deaths in 2018 [1]. Despite of the advances made for diagnosis at the early
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