mir-451a-5p Modulates Breast Cancer Cell Apoptosis, Migration, and Chemosensitivity to Carboplatin through the PTEN Pathway

Background: MicroRNAs (miRNAs) can play essential roles in the modulation of cancer cell growth, survival, and resistance to chemotherapy. Thus, we hypothesized that restoration of miR-451a-5p (a tumor suppressor) might affect sensitivity to chemotherapeutics in breast cancer cells. Methods: For this purpose, malignant breast cancer cells (MDA-MB-231) were transfected with miR-451a-5p mimic and exposed with carboplatin. Then, the apoptotic rate was evaluated by flow cytometry and DAPI staining (apoptosis), q-RT-PCR (expression levels of caspase-3, caspase-8, MMP9, ROCK, vimentin, c-Myc genes). Moreover, the proliferation and migration of cancer cells were assessed by MTT (cell viability) and wound healing assay. The western blot assay was used for protein expression of PTEN, AKT, and P-AKT. Results: Our findings demonstrated that a combination of miR-451a-5p restoration with carboplatin administration could additionally induce apoptosis, repress the proliferation and migration, and also increase PTEN protein expression with no significant alteration on the AKT/P-AKT protein expressions in the breast cancer cells. The present data was analyzed using GraphPad Prism 6 software by non-parametric one-way ANOVA and t-test. Conclusion: In conclusion, it seems that overexpression of miR-451a can enhance the chemosensitivity of breast cancer cells to carboplatin therapy. Thus, it may shed new light on miR-451a management of breast cancer chemoresistance and may be a beneficial strategy for future cancer therapy. However, further studies, particularly in other signaling pathways, should be required

Investigation of the Effect of miR-146a-5p on Expression of MMP9 Gene in Colorectal Cancer Cell Line (HT-29)

Backgrounds & objectives: Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. Micro RNAs are a group of non-coding small RNAs that inhibit the translation of target mRNA. MiR-146a-5p, as a tumor suppressor, has abnormal expression in many cancers. In this basic research, our goal was to restore the expression level of miR-146a-5p to normal level and to investigate its effect on the expression of the MMP9 gene in HT-29 cells. Methods: this study evaluates the effect of transfection of miR-146a-5p in HT-29 cell line. At first, the HT-29 cell line from colorectal cancer was cultured in RPMI-1640 culture media and then  were transfected with miR-146a-5p using Jet-PEI reagent. qRT-PCR technique was employed to evaluate the expression level of miR-146a-5p and MMP9 genes. The statistical analysis was performed using GraphPad Prism 6 software. Results: According to the obtained data, the onset of the invasion and metastasis, in particular, at the final stage of colorectal cancer may be related to a reduction in the expression of miR-146a-5p. The results of the qrRT-PCR test showed that by increasing the expression level of miR-146a-5p in HT-29 cells, the expression level of MMP9 gene decreased in the miR-146a-5p transfected group compared to the control group. Conclusions: According to this study, activation of metastatic pathways was due to the down regulation of miR146a-5p. Accordingly, miR-146a-5p can inhibits migration of these cells through down-regulating the expression of metastasis-related genes. Hence, miR-146a-5p can be a new diagnostic biomarker and new therapeutic target for CRC

The impact of microRNAs on myeloid-derived suppressor cells in cancer

Inflammation promotes cancer development. To a large extent, this can be attributed to the recruitment of myeloid-derived suppressor cells (MDSCs) to tumors. These cells are known for establishing an immunosuppressive tumor microenvironment by suppressing T cell activities. However, MDSCs also promote metastasis and angiogenesis. Critically, as small non-coding RNAs that regulate gene expression, microRNAs (miRNAs) control MDSC activities. In this review, we discuss how miRNA networks regulate key MDSC signaling pathways, how they shape MDSC development, differentiation and activation, and how this impacts tumor development. By targeting the expression of miRNAs in MDSCs, we can alter their main signaling pathways. In turn, this can compromise their ability to promote multiple hallmarks of cancer. Therefore, this may represent a new powerful strategy for cancer immunotherapy.</p