miR-330 Regulates Colorectal Cancer Oncogenesis by Targeting BACH1

Abstract

Purpose : Based on WHO report, colorectal cancer (CRC) is the second cause of death among patients with cancer worldwide. Dysregulation of miRNAs expressions has been demonstrated in different human cancers, especially CRC. Studies have shown that miR-330 could act as both TS-miR and/or oncomiR in different types of cancers. BACH1 is also identified as a transcription factor, which is involved in ontogenesis. In this study, we evaluated the CRC suppression via silencing of BACH1 by small silencer molecule called miR-330. Methods: Firstly, we analyzed the BACH1, miR-330-3p and miR-330-5p expressions according to the colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) project established from a patient of the colon and rectal cancer patients in The Cancer Genome Atlas (TCGA) database. The targeting of BACH1 via miR-330 in human CRC cells was evaluated by Vejnar bioinformatics methods, and confirmed by qRT-PCR and western blot analysis. Proliferation was performed by MTT assay. The MMP9, CXCR4, and VEGFR proteins were measured by western blotting. Results: The analysis of BACH1, miR-330-3p, and miR-330-5p expressions according to the COAD and READ projects showed that BACH1 was overexpressed, but miR-330-3p and miR330-5p were reduced in CRC tumors compared to normal controls. The miR-330 induction prevented proliferation of CRC cell by targeting BACH1 mRNA, which represses MMP9, C-X-C chemokine receptor type 4 (CXCR4), and vascular endothelial growth factor receptor (VEGFR) proteins expressions. Conclusion: Our results suggested that BACH1 is a potential target for miR-330 in CRC cells. The miR-330 induction inhibits CRC cells proliferation by suppressing BACH1 expression in posttranscriptional level. It was suggested that targeting of BACH1 via miRNA such as miR-330 could be a valid strategy in the field of CRC targeted therapy via modulating the oncogenic signaling pathway.

A Novel Therapeutic Target, BACH1, Regulates Cancer Metabolism

“…MicroRNA (miRNA) is a small non-coding RNA fragment consisting of about 22 nucleotides for negative regulation of genes by interacting with the 3′ UTR of target genes [ 30 ]. BACH1 is also regulated by miRNA-155 or miRNA-330 for proliferation and migration of renal cancer cells or colon cancer [ 31 , 32 ]. Likewise, Bach1 is regulated by numerous factors in non-tumor tissues.…”

A Novel Therapeutic Target, BACH1, Regulates Cancer Metabolism

“…MicroRNA (miRNA) is a small non-coding RNA fragment consisting of about 22 nucleotides for negative regulation of target genes by interacting with the 3' untranslated region (UTR) regions of genes [35]. BACH1 is also regulated by miRNA-155 or miRNA-330 for proliferation and migration of renal cancer cells or colon cancer [36,37]. Likewise, Bach1 is regulated by numerous factors in non-tumor tissues.…”

BTB and CNC homology 1 (Bach1) induces lung cancer stem cell phenotypes by inducing CD44 expression

“…Tumor volume was recorded every three days. 18 F-FDG PET/CT was carried out at 4 weeks after tumor cell injection to monitor the tumor growth. After PET/CT imaging, mice were sacri ced to harvest the tumor tissues for haematoxylin and eosin (HE) staining or IHC analysis.…”

“…For example, in breast cancer, Bach1 functions as an inducer of metastatic genes including CXCR4 and MMP1 [15,16]. The level of Bach1 indicates a higher risk of human cancers, such as colorectal cancer, glioblastoma and lung cancer [17][18][19]. Bach1 stabilization by antioxidants can induce lung cancer [20].…”