BC is the most common invasive cancer and the main leading cause of cancer death in women . The exact mechanism of BC, because of its heterogeneity and complexity, is unclear. Therefore, it is required to identify novel diagnostic and prognostic biomarkers. Recently, microRNAs are considered to paly critical roles in the development of BC as critical molecular regulators . Shifting of metabolism pathways is a significant property of breast cancer subtypes. Therefore, studying the metabolism profile can be a valuable approach to control cancer cells .
Glutamine is a necessary nutrient required for the growth and survival of a potentially large subset of tumors such as breast cancer . However, the role of glutamine metabolism on proliferation of breast cancer is still unknown. Recently, targeting cancer metabolism, especially inhibition of metabolic enzymes which are pivotal in cancer development, can be a great strategy in developing anti-cancer therapy. Glutaminase (GLS) as a crucial enzyme, which catalyzes the conversion glutamine to glutamate, may be a target in control cancer. Based on evidence, miRNAs play an important role in the regulation of cell metabolism . According to bioinformatics databases, miRNAs such as mir-513c and miR-3163 are involved in glutamine metabolism which have been evaluated in this study.
Based on recent evidences, the downregulation of mir-513c in multiple cancers and tumor suppressor role of miR-513c has been proved. In hepatocellular carcinoma, FLVCR1-AS1 as a lncRNA which its expression is associated with cancer properties such as apoptosis, migration, invasion and proliferation. FLVCR1-AS1 by directly sponging mir-513c leads to upregulate MET in HCC. Therefore, mir-513c through targeting MET prevented proliferation cancer cells . In neuroblastoma, mir-513c is markedly downregulated. Furthermore, mir-513c as a tumor suppressor, plays an important role in regulating glutamine metabolism through targeting GLS . Additionally, in glioblastoma (GBM) miR-513c was significantly downregulated. the Wnt/β-catenin is a critical pathway signaling in GBM progression . Low-density lipoprotein (LDL) receptor-related protein-6 (LPR6) is a key component of the LRP5/LRP6/Frizzled complex that is involved in activation of Wnt/β-catenin. Bioinformatics studies have proved LPR6 is a potential target of mir-513c. Therefore, mir-513c as a tumor suppressor may inhibit the proliferation of cancer cells in GBM .
Since the role of miR-513c-5p has not been fully understand, a bioinformatics analysis was done to shed the light on molecular pathways and biological procedures that are potentially effected by dysregulation of miR-513c-5p. In-silico studies proved that target genes of miR-513c are involved in pathways related to cancer progression. In the present study, miR-513c was relatively downregulated in BC tissues compared with margin tissues. Based on our research, several studies have been carried out on mir-513c but this is the first study that was done on breast cancer cell line and clinical samples. Our findings, similar to previous studies, showed decreased expression of mir-513c. Therefore, it seems mir-513c as a tumor suppressor may be a biomarker for prognosis and diagnosis of patients with breast cancer.
In several studies, the activity and expression of mir-3163 in multiple cancers such as NSCLC and Retinoblastoma (RB) have been evaluated. In NSCLC, mir-3163 as a moderator contributes to Meg3 to suppress and regulate the translation of skp2. However, the mir-3163 expression do not differ in NSCLC compared with normal cells, which suppresses the skp2 translation and reduction of its level in corporation with Meg3 to decrease cell proliferation in NSCLC . Retinoblastoma (RB) is the most common eye malignancy of childhood . Multidrug resistance is a significant problem in the treatment failure in RB . Based on new investigations, ABCG2 as an important contributing agent to multidrug resistance  is a potential target of mir-3163. Therefore, upregulation of mir-3163 suppressed ABCG2 expression, which subsequently reduced the multidrug resistance and promotion of apoptosis in RCSC .
Meanwhile, because the activity of miR-3163 has not been completely comprehended bioinformatics analysis was performed in cancers to determine the relationship between cancer and miR-3163. This analysis provides an insight into molecular pathways and biological processes that are potentially regulated by target gene of miR-3163. Among multiple significant pathways influence by miR-3163, MAPK signaling pathway, Hedgehog signaling pathway, Wnt signaling pathway are of most important and might obtain a valuable clue for connection between miR-3163 and breast cancer. MAPK signaling pathway is a critical key regulator in cellular functions, like cell differentiation, proliferation, differentiation, survival and apoptosis. The higher MAPK expression in subtypes of BC leads to invasive phenotypes and poor prognosis [29–31]. Hedgehog signaling pathway is another signaling pathways that constitutively dysregulated in BC cells. Also, this pathway plays a critical role in the development of BC . MiR-3163 is also related to the Wnt signaling that has a significant role in several biological processes. It has been proved that dysregulation of Wnt signaling leads to the progression of BC .
In the present study, our data contrary to previous studies have proved that the expression of mi-3163 was relatively downregulated in BC tissues compared with margin tissues. Recent reports have shown that miR-3163 plays diverse roles in various cancers; nonetheless, further studies are needed to identify the precise role of this microRNA. Based on our data and bioinformatics analysis, it seems that miR-3163 as a tumor suppressor may act as a biomarker in the prediction and diagnosis of patients with BC. Overall, based on our analysis, no significant association was found between miR-513c and miR-3163 expression and variables such as age, cancer family history, abortion.