A miR-124/ITGA3 axis contributes to colorectal cancer metastasis by regulating anoikis susceptibility.

Metastasis is the major cause for the death of patients with colorectal cancer (CRC). Anoikis resistance enhances the survival of cancer cells during systemic circulation, thereby facilitating secondary tumor formation in distant organs. miR-124 is a pleiotropically tumor suppressive small non-coding molecule. However, its role and mechanism in the regulation of cancer cell anoikis are still unknown. Here, we found that overexpression of miR-124 promotes anoikis of CRC cells in vitro and in vivo. In silico analysis and the experimental evidence supported that ITGA3 is a bona fide target of miR-124. Moreover, we identifies that ITGA3 plays a critical role in the regulation of anoikis sensitivity in CRC cells. Finally, our analysis in TCGA datasets demonstrates that high levels of ITGA3 are closely associated with poor prognosis in CRC patients. Collectively, we establish a functional link between miR-124 and anoikis susceptibility and provide that a miR-124/ITGA3 axis could be a potential target for the treatment of metastatic CRC.

FOXM1 promotes proliferation in human hepatocellular carcinoma cells by transcriptional activation of CCNB1.

The transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in cancer development and progression, including human hepatocellular carcinoma (HCC). However, the regulatory role and underlying mechanisms of FOXM1 is still limited. Here, we found that the high level expression of FOXM1 and CCNB1 is closely associated with poor prognosis in HCC patients. And FOXM1 and CCNB1 were overexpressed concomitantly in liver tumor tissues. Knockdown of FOXM1 significantly inhibited the expression levels of CCNB1 in HCC cell lines at both the mRNA and protein levels. Mechanistic studies revealed that FOXM1 binds directly to the promoter region of CCNB1 and regulates the expression levels of the CCNB1 gene in the transcriptional level. Furthermore, the loss of functional and rescue experiments showed that CCNB1 is essential for FOXM1-driven proliferation in HCC cells. In the present study, our results partially explained the dysregulated expression of FOXM1 play an important role in proliferation of human hepatocellular carcinoma cells via transcriptional activation of CCNB1 expression. And it also highlights a FOXM1/CCNB1 axis could be a potential target for the treatment of HCCs.

MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha.

The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3'-untranslated region (3'UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment.