MicroRNA-223 Targeting STIM1 Inhibits the Biological Behavior of Breast Cancer

Abstract

Background/Aims: To investigate the cellular effects and clinical significance of microRNA-223 (miR-223) in breast cancer by targeting stromal interaction molecule1 (STIM1). Methods: Breast cancer cell lines (T47D, MCF-7, SKB-R3, MDA-MB-231 and MDA-MB-435) and a normal breast epithelial cell line (MCF-10A) were prepared for this study. MiR-223 mimics, anti-miR-223 and pcDNA 3.1-STIM1 were transiently transfected into cancer cells independently or together, and then RT-qPCR was performed to detect the expressions of miR-223 and STIM1 mRNA, dual-luciferase reporter assay was conducted to examine the effects of miR-223 on STIM1, Western blotting was used to measure the expressions of the STIM1 proteins, MTT and Trans-well assays were performed to detect cell proliferation and invasion. Finally, the correlation of miR-223 and STIM1 was investigated by detecting with ISH and IHC in breast cancer specimens or the corresponding adjacent normal tissues. Results: Compared with normal cells and tissues, breast cancer tissues and cells exhibited significantly lower expression of miR-223, but higher expression of STIM1. MiR-223 could inhibit the proliferation and invasiveness of breast cancer cells by negatively regulating the expressions of STIM1. Reimplantation with STIM1 partially rescued the miRNA-223-induced inhibition of breast cancer cells. Clinical data revealed that high expression of STIM1 and miR-223 was respectively detrimental and beneficial factor impacting patient’s disease-free survival (DFS) rather than overall survival (OS). Moreover, Pearson correlation analysis also confirmed that STIM1 was inversely correlated with miR-223. Conclusion: MiR-223 inhibits the proliferation and invasion of breast cancer by targeting STIM1. The miR-223/STIM1 axis could possibly be a potential therapeutic target for treating breast cancer patients.

Low serum miR‐223 expression predicts poor outcome in patients with acute myeloid leukemia

“…24 The miR-223 levels were lower in breast cancer tissues and cells than those in normal tissues and cells, due to the fact that enforced miR-223 expression exhibited multiple anti-oncogenic effects in BC cells through silencing STIM1 expression. 25 In contrast, several studies had found high miR-223 expression in some cancers. In gastric cancer, upregulation of miR-223 more frequently occurred in tissues, cisplatin-resistant cells, and metastatic cells of gastric cancer, and high miR-223 expression markedly increased cancer cell metastasis, as well as stimulated cisplatin-induced apoptosis of resistant cells.…”

“…Compared with normal controls and chronic liver disease patients, patients with hepatocellular carcinoma exhibited significantly lower miR‐223 expression, indicating this miRNA had potential as an oncogene in hepatocellular carcinoma . The miR‐223 levels were lower in breast cancer tissues and cells than those in normal tissues and cells, due to the fact that enforced miR‐223 expression exhibited multiple anti‐oncogenic effects in BC cells through silencing STIM1 expression …”

“…MicroRNAs (miRNAs) are a class of single strand, small, and non-coding RNAs with highly conserved sequences about [18][19][20][21][22][23][24][25] nucleotides in length. MiRNAs are known to play an important role in multiple biological processes, such as cell growth, differentiation, apoptosis, and tumor angiogenesis.…”

Therapeutic potential of microRNAs in osteoporosis function by regulating the biology of cells related to bone homeostasis

“…M. Gao et al, 2018;He et al, 2018;Hummel et al, 2011;Lang & Zhao, 2018;Liao et al, 2018;Nicolè, Cappellesso, Sanavia, Guzzardo & Fassina, 2018;Q. Shi et al, 2017;Tan et al, 2017;Wang et al, 2018; L. Xu, Liu, Zhou, Chen, & Zhao, 2016;Yang et al, 2018;Zheng, Liu, Qiao, Zhang, & Lu, 2017;Zhu et al, 2016). These results are shown in Table 7.…”

The Calcium-Signaling Toolkit in Cancer: Remodeling and Targeting

“…Note that not all targets have been assessed in vivo or using pharmacological agents. TRPA1(Takahashi et al 2018), TRPC1 (El Hiani et al 2009; Faouzi et al 2016; Schaar et al 2016), TRPC3 (Zhang et al 2012), TRPC5 (Ma et al 2012, 2014; Zhu et al 2015), TRPC6 (Aydar et al 2009), TRPM2 (Hopkins et al 2015; Koh et al 2015; Gershkovitz et al 2018a,b,c), TRPM7 (Guilbert et al 2009; Kim 2012; Davis et al 2014a), TRPV1 (Weber et al 2016), TRPV4 (Fiorio Pla et al 2012; Lee et al 2016; Peters et al 2017), TRPV6 (Bolanz et al 2008; Peters et al 2012), ORAI1(Yang et al 2009;Feng et al 2010;Badaoui et al 2018;Liu et al 2018b), ORAI3(Faouzi et al 2013;Motiani et al 2013;Hasna et al 2018), STIM1(Yang et al 2009(Yang et al , 2018, MCU(Curry et al 2013;Tosatto et al 2016), IP 3 R3(Szatkowski et al 2010;Mound et al 2017), Ca V 3.1 (Ohkubo and Yamazaki 2012), PMCA2 (VanHouten et al 2010; Curry et al 2016; Peters et al 2016), PMCA4 (Curry et al 2012), PIEZO1 (Li et al 2015), and PIEZO2 (Pardo-Pastor et al 2018). S.J.…”