Long non-coding RNA BCYRN1 exerts an oncogenic role in colorectal cancer by regulating the miR-204-3p/KRAS axis

Abstract

Background It has been well documented that long non-coding RNAs (lncRNAs) regulate numerous characteristics of cancer, including proliferation, migration, metastasis, apoptosis, and even metabolism. LncRNA BCYRN1 (BCYRN1) is a newly identified brain cytoplasmic lncRNA with 200 nucleotides that was discovered to be highly expressed in tumour tissues, including those of hepatocellular carcinoma, gastric cancer and lung cancer. However, the roles of BCYRN1 in colorectal cancer (CRC) remain obscure. This study was designed to reveal the role of BCYRN1 in the occurrence and progression of CRC. Methods RT-PCR was used to detect the expression level of BCYRN1 in tumour tissues and CRC cell lines. BCYRN1 was knocked down in CRC cells, and cell proliferation changes were evaluated by cell counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), and Ki-67 and proliferating cell nuclear antigen (PCNA) expression assays. Cell migration and invasion changes were evaluated by wound healing, Transwell and invasion-related protein expression assays. Flow cytometry analysis was used to assess whether BCYRN1 regulates the apoptosis of CRC cells. The dual luciferase reporter gene detects the competitive binding of BCYRN1 to miR-204-3p. In vivo experiments were performed to evaluate the effect of BCYRN1 on tumour development. TargetScan analysis and dual luciferase reporter gene assays were applied to detect the target gene of miR-204-3p. Rescue experiments verified that BCYRN1 affects CRC by regulating the effect of miR-204-3p on KRAS. Results We found that compared with normal tissues and human intestinal epithelial cells (HIECs), CRC tumour tissues and cell lines had significantly increased BCYRN1 levels. We further determined that knockdown of BCYRN1 inhibited the proliferation, migration, and invasion and promoted the apoptosis of CRC cells. In addition, bioinformatics analysis and dual luciferase reporter assay showed that BCYRN1 served as a competitive endogenous RNA (ceRNA) to regulate the development of CRC through competitively binding to miR-204-3p. Further studies proved that overexpression of miR-204-3p reversed the effects of BCYRN1 on CRC. Next, TargetScan analysis and dual luciferase reporter assay indicated that KRAS is a target gene of miR-204-3p and is negatively regulated by miR-204-3p. A series of rescue experiments showed that BCYRN1 affected the occurrence and development of CRC by regulating the effects of miR-204-3p on KRAS. In addition, tumorigenesis experiments in a CRC mouse model confirmed that BCYRN1 downregulation effectively inhibited tumour growth. Conclusions Our findings suggest that BCYRN1 plays a carcinogenic role in CRC by regulating the miR-204-3p/KRAS axis.

The role of non-coding RNAs in chemotherapy for gastrointestinal cancers

“…Moreover, BCYRN1 also has a role in smooth muscle cell differentiation and vascularization within the cardiovascular system. 461,462 Yang et al 463 463 Taurine upregulated gene 1 (TUG1) was initially characterized as a transcript that was overexpressed in the presence of taurine, and then found to be a lncRNA with a role in embryonic retinal growth. 464 Moreover, TUG1 overexpression was detected in gastric, bladder, and cervical cancer.…”

“…Yang et al. 463 measured the expression levels of BCYRN1 in CRC tumor tissues and cell lines using RT-PCR. They used BCYRN1 knockdown in CRC cells to measure proliferation by 5-ethynyl-2′-deoxyuridine (EdU), CCK-8, and expression of proliferating cell nuclear antigen (PCNA) and Ki-67.…”

“…Therefore, BCYRN1 modulates the KRAS/miR-204-3p axis and plays a tumor promoter function in CRC. 463 …”

Genetic Mutations and Non-Coding RNA-Based Epigenetic Alterations Mediating the Warburg Effect in Colorectal Carcinogenesis

“…The ncRNAs mediate transcriptional regulation on an epigenetic level through interaction with chromatin modifiers, either directly via chromatin looping or by sponging a diversity of miRNAs [ 36 ]. Recently, accumulating evidence has also proven the role of regulatory ncRNA in metabolic remodeling of CRC [ 37 , 38 , 39 ]. These molecules can either function as tumor inducers or suppressers by targeting different players of CRC metabolism genes such as transcription factors, enzymes, and transporters of glycolysis.…”

“…Epigenetic alteration of KRAS has been observed to modulate different cellular pathways and delay CRC progression [ 39 ]. However, the epigenetic alteration of KRAS that affects its role in glycolysis is still unclear.…”