MiR-199a/b-3p inhibits colorectal cancer cell proliferation, migration and invasion through targeting PAK4 and BCAR3

Abstract

Background Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. P21 activated kinase 4 (PAK4) and Breast cancer anti-estrogen resistance 3 (BCAR3) have been reported to be involved in numerous aspects in tumorous progression. In this study, we propose to screen multi-targeted microRNAs. (miRNAs), which simultaneously inhibit neoplastic evolution through suppressing the transcription of target genes. Methods MTT and Colony formation assays measured cell’s viability and proliferation. Scratch wound and Transwell assays detected the ability in migration and invasion for SW116 cells. The multi-targeted microRNAs of PAK4 and BCAR3 were predicted using bioinformatics analysis and verified by conducting dual luciferase reporter assay, western blot and qRT-PCR that could detect the expression levels of miR-199a/b-3p. Results The knockdown of PAK4 significantly impeded proliferation and colony formation of SW1116 cells when the knockdown of BCAR3 hindered migration and invasion of SW1116 cells. MiR-199a/b-3p directly targeted the 3'-UTR of PAK4 and BCAR3, further effected proliferation, colony formation, migration, and invasion of SW1116 cells. PAK4 or BCAR3 overexpression could partially reversed inhibitory effects of miR-199a/b-3p. Conclusions These results provided a new multi-targeted cite for cancerous suppressant to improve the prognosis of CRC inpatients.

miR-199a/b-3p inhibits HCC cell proliferation and invasion through a novel compensatory signaling pathway DJ-1\Ras\PI3K/AKT

“…A large number of studies have shown that miR-199a/b-3p is a tumor suppressor gene, which can inhibit the proliferation, invasion and drug resistance of tumor cells such as gastric cancer 32 , HCC 33 – 37 , breast cancer 38 , colorectal cancer 39 and other tumor cells by regulating PAK4/MEK/ERK, PAK4/BCAR3 and other signaling pathways 55 , 56 . Our analysis of TCGA data showed that the expression of miR-199a/b-3p in HCC tissue samples was significantly lower than that in adjacent tissues, and the results of HCC diagnostic ROC curve analysis also showed that miR-199a/b-3p had predictive value for HCC diagnosis.…”

“…miR-199a/b-3p, which is a tumor suppressor gene, can inhibit the proliferation of gastric cancer 34 , HCC 35 – 38 , breast cancer 40 , colorectal cancer 41 , and prostate cancer 42 by regulating the PAK4/MEK/ERK signaling pathway. Additionally, it has been found miR-199a/b-3p can inhibit HCC growth, apoptosis, invasion and angiogenesis via multiple targets, such as PDCD4, CD44, CD151, VEGFA AEGFR1/2, HGF and MMP2 35 – 38 and can affect the chemical sensitivity of hepatoma cells to doxorubicin via mTOR and c-Met 39 . What's more interesting to us is that DJ-1 might be a promising target gene for miR-199a/b-3p and intersect with the Ras and PI3K/AKT signaling pathways through analysis of miRWalk, TargetScan, and TGCA databases.…”

BCAR3 and BCAR3-related competing endogenous RNA expression in hepatocellular carcinoma and their prognostic value

“…BCAR3 played an important role in the metastasis and invasion of breast cancer cells and promoted the proliferation and migration of triple-negative breast cancer by regulating MET signaling[ 6 , 7 ]. The experiment by Hou et al [ 8 ] confirmed that BCAR3 knockout significantly inhibited cell migration and colorectal cancer cell invasion, but did not affect tumor cell proliferation. In contrast, high BCAR3 expression was strongly associated with a better prognosis in multiple myeloma[ 9 ].…”