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

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. 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. 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. These results provided a new multi-targeted cite for cancerous suppressant to improve the prognosis of CRC inpatients.

Hou J ，Mi X ，Liu N ，Li X ，Li XN ，Yang Y ，Lu X ，Fang Y ，Jin NY ... -  《-》

MiR-199a/b-3p suppresses migration and invasion of breast cancer cells by downregulating PAK4/MEK/ERK signaling pathway.

MicroRNA-199a/b-3p is downregulated in several types of aggressive cancer, and its decrement significantly correlates with poor survival. Here, we aim to investigate the biological function of miR-199a/b-3p and its regulation of target genes in breast cancer cells with highly metastatic potential. In addition, we found that miR-199a/b-3p expression was much lower in MDA-MB-231, CAL120, and HCC1395 breast cancer cells with highly metastatic potential. Functional assays showed that restored miR-199a/b-3p expression inhibited MDA-MB-231 cell growth, cell-cycle progression, migration, and invasion. In addition, we experimentally demonstrated that PAK4 was the direct target of miR-199a/b-3p, hypo-expression of PAK4 suppressed proliferation, migration and invasion of MDA-MB-231 cells, and overexpression of PAK4 significantly rescued the inhibitory effect of miR-199a/b-3p on MDA-MB-231 cell growth, migration, and invasion. Further, we also observed that miR-199a/b-3p could inactivate the PAK4/MEK/ERK signaling pathway. Thus, miR-199a/b-3p functions as a tumor suppressor and has an important role in breast cancer metastasis through PAK4/MEK/ERK signaling pathway.

Li SQ ，Wang ZH ，Mi XG ，Liu L ，Tan Y ... -  《-》

PAK4, a target of miR-9-5p, promotes cell proliferation and inhibits apoptosis in colorectal cancer.

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. P21-activated kinase 4 (PAK4) and miR-9-5p have emerged as attractive therapeutic targets in several tumor types, but in CRC, the regulation of their biological function and their target association remain unclear. The expression of PAK4 in CRC tissues was determined using quantitative real-time PCR and immunohistochemistry analyses. The targeted regulation between miR-9-5p and PAK4 was predicted and confirmed with bioinformatics analysis and the dual-luciferase reporter assay. Functional experiments, including the MTT assay and flow cytometry, were performed to investigate the impact of PAK4 knockdown and miR-9-5p overexpression on cell proliferation and apoptosis in CRC cells. We found that the expression of PAK4 was upregulated in CRC tissues. PAK4 knockdown significantly suppressed cell proliferation and promoted apoptosis in cells of the CRC cell lines HCT116 and SW1116. We also found that miR-9-5p directly targeted the 3'-UTR of PAK4 mRNA and negatively regulated its expression. The degree of downregulation of miR-9-5p inversely correlated with PAK4 expression. Intriguingly, enforced expression of miR-9-5p suppressed cell proliferation and promoted apoptosis. This could be partially reversed by PAK4 overexpression. These results suggest that miR-9-5p targeting of PAK4 could have therapeutic potential for CRC treatment.

Wang M ，Gao Q ，Chen Y ，Li Z ，Yue L ，Cao Y ... -  《-》

MiR-199a/b-3p inhibits gastric cancer cell proliferation via down-regulating PAK4/MEK/ERK signaling pathway.

Zeng B ，Shi W ，Tan G 《BMC CANCER》

LncRNA IGFL2-AS1 as a ceRNA Promotes HCT116 Cell Malignant Proliferation via the miR-433-3p/PAK4 Axis.

Liu S ，Wang X ，Zhang J ，Liu Y ，Li B ... -  《-》