“…The downregulation was also observed in the BC cell lines compared with MCF-10A (epithelial cells), and interestingly the levels of miR-613 in the triple negative breast cancer (TNBC) more invasive cell line (MDA-MB-231) were significantly lower than the non-TNBC counterpart (MCF-7). All of these findings are consistent with the previous studies (Xiong et al, 2018;Liu et al, 2020;Li et al, 2021).…”
Section: Discussionsupporting
confidence: 93%
“…NAMPT has been introduced as a key regulator of BC growth and metastasis (Sheikhpour, 2017). MiRs have recently been proposed to be involved in tumorigenesis and progression of BC; therefore, they could be considered as an innovative tool for diagnosis and treatment of BC (Hesari et al, 2018;Liu et al, 2020;Peng et al, 2020;Shibuya et al, 2020;Li et al, 2021). We previously presented miRNAs as effective tools to promote apoptosis and reduce cell viability in BC cells by inhibiting NAMPT activity and subsequently decreasing NAD levels (Alaee et al, 2017;Hesari et al, 2018;Bolandghamat Pour et al, 2019a, FIG. 3.…”
Section: Discussionmentioning
confidence: 99%
“…More importantly, the majority of available studies indicate that miR-613 remarkably suppresses the expression of oncogenes and malignant features of tumors meaning that it plays a tumor-suppressive role in several neoplasms (Mei et al, 2020). Notably, a pile of recently published articles suggest that downregulation of miR-613 is tightly associated with BC progression, and its forced overexpression can restrain BC development (Liu et al, 2020;Zang et al, 2020).…”
NAD is mainly biosynthesized by the enzymatic action of nicotinamide phosphoribosyltransferase (NAMPT) through the salvage pathway. NAD is indispensable for the proper function and metabolism of all living cells, including cancer cells. Our previous researches revealed that inhibition of NAMPT by miRNA (miR) could suppress NAD levels and thereby hinder the growth and promotion of breast cancer (BC). Therefore, the current study was undertaken to investigate the inhibitory effects of miR-613 on NAMPT and BC cells' survival. Bioinformatics analysis and luciferase reporter assay confirmed that NAMPT 3¢-untranslated region is a direct target for miR-613. The expression of miR-613 was noticed to be significantly decreased in both clinical tissue samples and BC cells by real-time PCR. Following transfection with miR-613 mimic, the expression of miR-613 was elevated in the BC cells leading to inhibition of NAMPT expression at both mRNA and protein level as measured by real-time PCR and western blotting, respectively. Inhibition of NAMPT led to a remarkable reduction in the concentration of NAD in the BC cells NAMPT. The transfection also declined cell viability roughly 40% in MD Anderson-Metastatic Breast-231 (MDA-MB-231) cells. Consistently, the apoptosis rate was remarkably increased, around 65% in these cells as assayed by labeling the cells with Annexin Vfluorescein isothiocyanate (FITC) and Propidium Iodide. Targeting the NAMPT-mediated NAD salvage pathway by miR-613 is a novel approach for managing BC, which is worth further investigation.
“…The downregulation was also observed in the BC cell lines compared with MCF-10A (epithelial cells), and interestingly the levels of miR-613 in the triple negative breast cancer (TNBC) more invasive cell line (MDA-MB-231) were significantly lower than the non-TNBC counterpart (MCF-7). All of these findings are consistent with the previous studies (Xiong et al, 2018;Liu et al, 2020;Li et al, 2021).…”
Section: Discussionsupporting
confidence: 93%
“…NAMPT has been introduced as a key regulator of BC growth and metastasis (Sheikhpour, 2017). MiRs have recently been proposed to be involved in tumorigenesis and progression of BC; therefore, they could be considered as an innovative tool for diagnosis and treatment of BC (Hesari et al, 2018;Liu et al, 2020;Peng et al, 2020;Shibuya et al, 2020;Li et al, 2021). We previously presented miRNAs as effective tools to promote apoptosis and reduce cell viability in BC cells by inhibiting NAMPT activity and subsequently decreasing NAD levels (Alaee et al, 2017;Hesari et al, 2018;Bolandghamat Pour et al, 2019a, FIG. 3.…”
Section: Discussionmentioning
confidence: 99%
“…More importantly, the majority of available studies indicate that miR-613 remarkably suppresses the expression of oncogenes and malignant features of tumors meaning that it plays a tumor-suppressive role in several neoplasms (Mei et al, 2020). Notably, a pile of recently published articles suggest that downregulation of miR-613 is tightly associated with BC progression, and its forced overexpression can restrain BC development (Liu et al, 2020;Zang et al, 2020).…”
NAD is mainly biosynthesized by the enzymatic action of nicotinamide phosphoribosyltransferase (NAMPT) through the salvage pathway. NAD is indispensable for the proper function and metabolism of all living cells, including cancer cells. Our previous researches revealed that inhibition of NAMPT by miRNA (miR) could suppress NAD levels and thereby hinder the growth and promotion of breast cancer (BC). Therefore, the current study was undertaken to investigate the inhibitory effects of miR-613 on NAMPT and BC cells' survival. Bioinformatics analysis and luciferase reporter assay confirmed that NAMPT 3¢-untranslated region is a direct target for miR-613. The expression of miR-613 was noticed to be significantly decreased in both clinical tissue samples and BC cells by real-time PCR. Following transfection with miR-613 mimic, the expression of miR-613 was elevated in the BC cells leading to inhibition of NAMPT expression at both mRNA and protein level as measured by real-time PCR and western blotting, respectively. Inhibition of NAMPT led to a remarkable reduction in the concentration of NAD in the BC cells NAMPT. The transfection also declined cell viability roughly 40% in MD Anderson-Metastatic Breast-231 (MDA-MB-231) cells. Consistently, the apoptosis rate was remarkably increased, around 65% in these cells as assayed by labeling the cells with Annexin Vfluorescein isothiocyanate (FITC) and Propidium Iodide. Targeting the NAMPT-mediated NAD salvage pathway by miR-613 is a novel approach for managing BC, which is worth further investigation.
“…Being a hotspot for a long time, many miRNAs have been reported to involve in regulating the oncogenesis and progression of human cancers [ 32 – 34 ]. MiR-613 has been identified as a significant suppressor in multiple cancers, including gastric cancer [ 35 ], bladder cancer [ 36 ], and BrCa [ 37 ]. In BrCa, a penal of targets of miR-613 has been identified, including FAM83A [ 37 ], CDK12 [ 38 ], and HK2 [ 39 ].…”
Section: Discussionmentioning
confidence: 99%
“…MiR-613 has been identified as a significant suppressor in multiple cancers, including gastric cancer [ 35 ], bladder cancer [ 36 ], and BrCa [ 37 ]. In BrCa, a penal of targets of miR-613 has been identified, including FAM83A [ 37 ], CDK12 [ 38 ], and HK2 [ 39 ]. YWHAZ has been identified as the target gene of miR-613 in hepatocellular carcinoma [ 40 ].…”
Dishevelled-associated activator of morphogenesis 1 (DAAM1) is a critical driver in facilitating metastasis in breast cancer (BrCa). However, molecular mechanisms for the regulation of DAAM1 activation are only partially elucidated. In this research, the expression levels of YWHAZ and DAAM1 were examined by immunohistochemistry (IHC) staining in BrCa tissues. The functional roles of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ)–DAAM1 axis and their regulator microRNA-613 (miR-613) in BrCa cells and associated molecular mechanisms were demonstrated in vitro. As results, the expression levels of DAAM1 and YWHAZ were significantly upregulated in BrCa tissues compared with normal tissues and remarkably associated with poor prognosis. Besides, DAAM1 and YWHAZ were positively correlated with each other in BrCa tissues. YWHAZ interacted and colocalized with DAAM1 in BrCa cells, which was essential for DAAM1-mediated microfilament remodeling and RhoA activation. Moreover, miR-613 directly targeted both YWHAZ and DAAM1, contributing to inhibiting BrCa cells migration via blocking the complex of YWHAZ–DAAM1. To sum up, these data reveal that YWHAZ regulates DAAM1 activation, and the YWHAZ–DAAM1 complex is directly targeted by the shared post-transcriptional regulator miR-613.
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