Abstract
Increasing numbers of miRNAs have been observed as oncogenes or tumor suppressors in colorectal cancer (CRC). It was recently reported that hsa-miR-106b-5p (miR-106b) promoted CRC cell migration and invasion. However, there were also studies showing contradictory results. Therefore, in the present study, we further explore the role of miR-106b and its downstream networks in the carcinogenesis of CRC. We observed that the expression of miR-106b is significantly increased in Pan-Cancer and CRC tissues compared with normal tissues from The Cancer Genome Atlas (TCGA) database. Furthermore, we used Transwell, Cell Counting Kit-8, and colony formation assays to clarify that miR-106b promotes the migratory, invasive, and proliferative abilities of CRC cells. For the first time, we systematically screened the target mRNAs and lncRNAs of miR-106b using TCGA database and the bioinformatics algorithms. Dual-luciferase reporter assay confirmed that NR2F2-AS1 and PLEKHO2 are the direct targets of miR-106b. Furthermore, NR2F2-AS1 acts as a competing endogenous RNA (ceRNA) to regulate PLEKHO2 expression by sponging miR-106b. The results of Gene set enrichment analysis (GSEA) and Western blot indicated that they play important roles in CRC progression by regulating MAPK pathway. Thus, miR-106b/NR2F2-AS1/PLEKHO2/MAPK signaling axis may suggest the potential usage in CRC treatment.
Highlights
Colorectal cancer (CRC) is one of the most common malignant tumors and is the third leading cause of cancer-related deaths worldwide [1]
In order to prove that miR-106b is involved in tumorigenesis, we first analyzed miR-106b expression in Pan-Cancer from the The Cancer Genome Atlas (TCGA) dataset, and the result showed that the level of miR-106b in tumor tissues is significantly higher than that in normal tissues (Figure 1A)
We found that the expression of miR-106b in CRC tissues is higher than that in colorectal normal tissues from TCGA dataset (Figure 1B)
Summary
Colorectal cancer (CRC) is one of the most common malignant tumors and is the third leading cause of cancer-related deaths worldwide [1]. More and more evidence shows that the carcinogenesis of CRC is related to genetic mutations and epigenetic changes, the latter including non-coding RNA, such as microRNA (miRNAs), long non-coding RNA (lncRNAs) and DNA methylation, etc. It was recently reported that hsa-miR-106b-5p (miR-106b) promoted CRC cell migration and invasion by targeting DLC1 gene [6]. Previous studies showed that miR-106b was significantly down-regulated in the stage III-IV of CRC tissues compared with the stage I-II, and miR-106b inhibited the migration and invasion of CRC cells [8]. In the present study, we will confirm and further explore the role of miR-106b in the carcinogenesis of CRC. We confirm that miR-106b promotes CRC cell migration and proliferation. We systematically screened the mRNA and lncRNA targets of miR-106b in CRC using The Cancer Genome Atlas (TCGA) database and bioinformatic analysis. Our findings may provide new insights into the role of miR-106b in the carcinogenesis of CRC
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have