MicroRNA-124 Inhibits The Biological Significance Of Breast Cancer Cell Growth

Breast cancer is the major cause of cancer-related deaths in women worldwide. Chemotherapy is one of the most important methods for breast cancer, and can relieve the clinical symptoms, prolong the survival period. However, the chemotherapy drug resistance is a big problem for people all over the world. As everyone knows, at the beginning of the chemotherapy, the tumors are more sensitive to drugs, but with the deepening of the treatment, tumor resistance has been turn up. So the tumor molecular mechanism of drug resistance is very important which can help us find a way to reverse tumor chemotherapy drug resistance. miRNAs were a length of 19-25 nucleotides of non-coding small RNAs, can complete or incomplete matching the 3 ’UTR of target gene mRNAs, making target mRNA degradation after transcription or translation inhibition. miRNAs can also participate in individual development, cell apoptosis, proliferation and differentiation physiological process. In recent years, several studies have shown some results on the association between miRNAs and chemosensitivity tumors. Ectopic expression of miR-34 can induce the sensitivity of p53-deficient human gastric cancer to chemotherapy. In addition, chemotherapy can reverse the miRNA expression and the sensitivity of tumor cells to chemotherapy drugs. Such as cisplatin can obviously decrease the expression of miR-30 in tumor cells, at.the same time significantly suppress the apoptosis induced by cisplatin. There have been very complex feedback loop between miRNAs and chemotherapy drug resistance.Studies have confirmed that miR-124 expression was significantly downregulated in breast cancer, cervical cancer and liver cancer cell lines and patient specimen, compared with normal cell lines and paired adjacent normal tissues, respectively. The ectopic expression of miR-124 inhibited cell growth, migration and invasion. miR-124 might be a tumor suppressor in breast cancer via the regulation of FLOT1. miR-124 can also inhibit cancer cell proliferation via the regulation of cell cycle protein kinase CDK6.Single-nucleotide polymorphisms (SNPs) in microRNAs gene may alter microRNA expression and maturation and may also further change the effects of microRNAs to their target genes. Common single nucleotide polymorphisms (SNPs) in pre-miRNAs and cancer risk has been investigated by case-control studies in the last decade, and some common SNPs in pre-miRNAs have been demonstrated with an increased cancer risk. In recent years, some case-control studies have been conducted to determine the association between miR124 rs531564 and multiple kinds of cancers in various types, such as Esophageal Cancer and Cervical Cancer.Therefore, miR-124 may be a tumor suppressor to involved in the tumor occurrence and development.1、The study on the breast cancer progression inhibited by miR-124 both in vitro and in vivoObjective:To investigate the effects of miR-124 on the growth inhibition of breast. cancer both in vitro and in vivo.Methods:Real time quantitative PCR (qRT-PCR) was used to detect the expression level of miR-124 in 40 cases of breast cancer specimens and normal tissue adjacent to carcinoma specimens, and three breast cancer cell lines. MTT was used to detect the growth inhibition of breast cancer cell lines after overexpress or silence the expression of miR-124. Tumor-burdened nude mice were used to test the role of miR-124 in breast cancer.Results:The results showed that the expression of miR-124 in breast cancer specimens was significantly lower than the normal tissue adjacent to carcinoma, as in the three breast cancer cell lines. After overexpressing or suppressing the expression of miR-124, the proliferation of breast cancer was suppressed or promoted. Further more, overexpression of miR-124 can effectively inhibit the growth of xenograft tumor in vivo.Conclusion:miR-124 can inhibit the proliferation of breast cancer in vitro and in vivo, as a tumor suppressor.2、The effects of miR-124 on the proliferation inhibition of breast cancer cell MCF-7 induced by paclitaxelObjective:To investigate the. effects of miR-124 on the growth inhibition of breast. cancer cell MCF-7 induced by paclitaxel.Methods:MTT was used to detect the·growth inhibition of MCF-7 induced by paclitaxel. Flow cytometry was used to detect the effect of paclitaxel on cell cycle. Real time quantitative PCR(qRT-PCR) was used to detect the expression level of miR-124, while MCF-7 was treated with paclitaxel. MiR-124 inhibitor was transfected into MCF-7 breast cancer cell, and growth inhibition was detected by MTT.Results:The results showed that paclitaxel can significantly inhibit the cell growth of breast cancer cell MCF-7 by blocking the G2 phase. The results of qRT-PCR showed that the relative expression of miR-124 was increased when the dosage of paclitaxel was increased. While the expression of miR-124 was inhibited, the cell growth inhibition caused by paclitaxel was also prominent decreased.Conclusion:The higher expression of miR-124 in MCF-7 induced by paclitaxel was dose dependent. And miR-124 inhibitor can significant influence the cell growth inhibition caused by paclitaxel. These results indicated that miR-124 plays an important role in paclitaxel chemotherapy drug resistance, and provides a new way to solve the problem.’3、mir-124 rs531564 polymorphism and cancer risk:a meta-analysisBackground:Several studies have reported the role of the miR-124 rs531564 C> G polymorphism as a susceptibility factor for cancers. However, the results are conflicting rather than conclusive. Therefore, we conducted the present meta-analysis to obtain the most reliable estimate of the association.Methods:We conducted a literature search of Medline, Embase and Wangfang Medicine databases to identify all relevant studies in this meta-analysis. Crude odds ratios (ORs) with 95% confience intervals (CIs) were extracted and pooled to assess the strength of the association between miR-124 rs531564 C> G polymorphism and cancer risk. A total of four eligible studies including 2,003 cases and 2,429 controls based on the search criteria were included.Results:We found that the miR-124 rs531564 polymorphism was significantly associated with decreased risk of cancers in the allelic model (G vs. C, OR=0.71, 95% CI=0.53-0.94, P=0.02), homozygote model (GG vs. CC, OR=0.42,95% CI=0.26-0.66, P=0.0002), dominant model (GG/GC vs. CC, OR=0.71,95% CI=0.51-0.98, P=0.04) and recessive model (GG vs. GC/CC, OR=0.43,95% CI=0.27-0:69, P=0.0004). In the stratified analysis by Cervical Cancer group, significant associations were observed in the allelic model (G vs. C, OR=0.46,95% CI=0.32-0.66, P< 0.0001), heterozygote model (GC vs. CC, OR=0.47,95% CI=0.32-0.69, P=0.0001), homozygote model (GG vs. CC, OR=0.45,95% CI=0.26-0.76, P=0.003) and dominant model(GG/GC vs. CC, OR=0.45,95% CI=0.3-0.66, P< 0.0001). Subgroup analysis also revealed decreased risk for Esophageal Squamous Cell Carcinoma in homozygote model (GG vs. CC, OR=0.45, 95% CI=0.27-0.75, P=0.002) and recessive model (GG vs. GC/CC, OR=0.46,95% CI=0.28-0.75, P=0.002) by cancer type.Conclusions:’This meta-analysis suggests that the miR-124 rs531564 C> G polymorphism is an important risk factor for cancers in Chinese. However, well-designed studies with larger sample size are needed to further validate the results.