MiR-223-3p targeting SEPT6 promotes the biological behavior of prostate cancer

Wei, Yongbao; Yang, Jin; Lee, Yi; Wang, Yinhuai; Dong, Zhifeng; Liu, Ziting; Ou-yang, Shifeng; Wu, Hongtao; Zhong, Zhaohui; Yin, Zhu; Zhou, Ke-qin; Gao, Yunliang; Yan, Bin; Zhao, Wang

doi:10.1038/srep07546

Cited by 67 publications

(71 citation statements)

References 49 publications

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“…In particular, ZEB1 was proven to be suppressed by miR-223–3p in BC cell lines treated with Ginkgolide B 36. Furthermore, SEPT6 was reported to be specifically targeted by miR-223-3p in prostate cancer cell lines 37. Among miRNAs involved in inflammation, miR-17-5p deserves particular attention as member of miR-17/92 cluster involved in tumorigenesis, immune diseases, cardiovascular diseases, neurodegenerative diseases and aging 14.…”

Section: Discussionmentioning

confidence: 99%

Expression of urinary miRNAs targeting NLRs inflammasomes in bladder cancer

Mearini¹,

Poli

Cochetti³

et al. 2017

OTT

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Aim of the studyInflammasome, a large complex of NOD-like receptors (NLRs), drives tumor growth and progression. The present study aimed at exploring the alteration in expression of urinary inflammasome-related microRNAs (miRNAs) in bladder cancer (BC). Our previous report demonstrated the up-regulation of NLRs genes (NLRP3, NLRP4, NLRP9 and NAIP) in urine sediments of patients harboring BC. The expression levels of miRNAs targeting these NLRs (miR-146a-5p, miR-106a-5p, miR-17-5p, miR-223-3p, miR-141-3p, miR-19a-3p, miR-145-5p, miR-185-5p) were assayed in the same patient cohort.Materials and methodsForty-six subjects affected by BC, 28 healthy controls (CTR0) and 31 subjects with histologically confirmed bladder inflammation (CTR1) were recruited. Total RNA was extracted from urine sediment and resulting cDNA was used for amplification by real-time polymerase chain reaction. MiRNA expression levels were evaluated and compared among selected groups. Patients were further stratified according to tumor stage, grade and risk of recurrence and progression. Moreover, non-muscle invasive low-grade and high-grade (HG) BC patients were compared.ResultsMiR 141-3p and miR-19a-3p expression decreased in CTR1 with respect to both BC and CTR0. In contrast, miR-146a-5p was up-regulated in BC compared with CTR0. MiR106a-5p, miR17-5p and miR19a-5p were significantly up-regulated in HG, high-risk (HR) and non-muscle invasive HG BC patients, while miR-185-5p was significantly higher in muscle invasive tumors, according to T stage stratification.ConclusionThe increased expression of miRNAs targeting NLRs in HG and HR BC patients is in accordance with the decrease in NLR mRNAs observed in our previous report. These data corroborate the direct role of NLR genes and respective regulatory miRNAs in BC making these inflammasome-related molecules a reliable non-invasive tool for BC diagnosis.

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Section: Discussionmentioning

confidence: 99%

Expression of urinary miRNAs targeting NLRs inflammasomes in bladder cancer

Mearini¹,

Poli

Cochetti³

et al. 2017

OTT

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“…Similarly, Li et al (2011) [24] shown that miR-223 was able to stimulate non-metastatic gastric cancer cells to invade by targeting a tumor suppressor gene named EPB41L3 . Wei et al (2014) [31] also found accelerated invasive ability of Prostate Cancer cell lines when miR-223-3p were artificially added to the cells, but in this case through SEPT6 targeting.…”

Section: Discussionmentioning

confidence: 99%

MiR-223-5p works as an oncomiR in vulvar carcinoma byTP63suppression

et al. 2016

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MiR-223-5p has been previously mentioned to be associated with tumor metastasis in HPV negative vulvar carcinomas, such as in several other tumor types. In the present study, we hypothesized that this microRNA would be important in vulvar cancer carcinogenesis and progression. To investigate this, we artificially mimicked miR-223-5p expression in a cell line derived from lymph node metastasis of vulvar carcinoma (SW962) and performed in vitro assays. As results, lower cell proliferation (p < 0.01) and migration (p < 0.001) were observed when miR-223-5p was overexpressed. In contrast, increased invasive potential of these cells was verified (p < 0.004). In silico search indicated that miR-223-5p targets TP63, member of the TP53 family of proteins, largely described with importance in vulvar cancer. We experimentally demonstrated that this microRNA is capable to decrease levels of p63 at both mRNA and protein levels (p < 0.001, and p < 0.0001; respectively). Also, a significant inverse correlation was observed between miR-223-5p and p63 expressions in tumors from patients (p = 0.0365). Furthermore, low p63 protein expression was correlated with deeper tumor invasion (p = 0.0491) and lower patient overall survival (p = 0.0494). Our study points out miR-223-5p overexpression as a putative pathological mechanism of tumor invasion and a promising therapeutic target and highlights the importance of both miR-223-5p and p63 as prognostic factors in vulvar cancer. Also, it is plausible that the evaluation of p63 expression in vulvar cancer at the biopsy level may bring important contribution on prognostic establishment and in elaborating better surgical approaches for vulvar cancer patients.

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“…However, other researchers found that overexpression of miR-223 was positively correlated with tumor recurrence and metastasis in patients with colorectal cancer [33], hepatocellular cancer [34] and non-small cell lung cancer [35]. Several in vitro studies also verified that miRNA-223 promoted lung cancer, ovarian cancer and prostate cancer cells invasion via targeting EPB41L3 [36] , SOX11 [37] and SEPT6 [38] respectively. These inconsistent results may be due to the different roles of the target genes of miRNA-223 in the tumor.…”

Section: Discussionmentioning

confidence: 99%

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

Yang¹,

Jiang

Ma³

et al. 2018

Cell Physiol Biochem

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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.

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MiR-223-3p targeting SEPT6 promotes the biological behavior of prostate cancer

Cited by 67 publications

References 49 publications

Expression of urinary miRNAs targeting NLRs inflammasomes in bladder cancer

Expression of urinary miRNAs targeting NLRs inflammasomes in bladder cancer

MiR-223-5p works as an oncomiR in vulvar carcinoma byTP63suppression

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

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