miR‐587 promotes cervical cancer by repressing interferon regulatory factor 6

Abstract

Background: Interferon regulatory factor 6 (IRF6) exhibits tumor-suppressive functions in several cancer types. In the present study, the antitumor properties and related pathway mechanism of IRF6 were investigated in cervical cancer. Methods: Forty-one pairs of cervical cancer specimens and para-carcinoma tissues were collected to evaluate IRF6 expression using immunohistochemical staining and miR-587. The effects of miR-587 and IRF6 on cervical cancer cell growth were explored by MTT assays and in a HeLa tumor xenograft mouse model. The migration and invasion of cervical cancer cells were monitored using transwell assays. Results: IRF6 expression in cervical cancer specimens and cell lines was significantly reduced compared to that in the corresponding control group. In addition, IRF6 expression was negatively correlated with miR-587 in cervical cancer tissues. Bioinformatics algorithms and luciferase assays revealed that IRF6 is a potential target of miR-587, and miR-587 mimic transfection led to a significant repression of IRF6 protein levels in cervical cancer cells. We also discovered that the antineoplastic properties of IRF6 could be reversed by overexpressing miR-587 in cervical cancer cells. The up-regulation of miR-587 was correlated with poor overall survival in cervical cancer. In an in vivo experiment, miR-587 silencing induced HeLa tumor growth inhibition, which was associated with the up-regulation of IRF6 protein in the tumor. Conclusions: miR-587 post-transcriptionally represses IRF6 protein expression to abrogate the antineoplastic activity of IRF6. The miR-587/IRF6 signaling pathway plays a crucial role in the progression of cervical cancer and serves as a potential therapeutic target for the treatment of cervical cancer. K E Y W O R D S cervical cancer, interferon regulatory factor 6, miR-587, prognosis 1 | INTRODUCTION Cervical cancer is one of the most common gynecologic malignant neoplasms and ranks fourth for both incidence and mortality in females. 1 According to an epidemiological investigation, cervical cancer accounted for approximately 6.6% of the total incidents and 7.5% of the total cancer deaths among females in 2018. 1 In general, persistent human papillomavirus infection can lead to intraepithelial lesions of the cervix uteri, which is an inevitable cancerous process of cervical cancer. 2,3 The mechanisms of cervical carcinogenesis are complicated. Different signaling pathways, such as nuclear factorkappa B, mammalian target of rapamycin, phosphoinositide 3-kinase Yuefang Ren and Jie Dong contributed equally to this work.

PGM5-AS1 impairs miR-587-mediated GDF10 inhibition and abrogates progression of prostate cancer

“…The oncomiR property of miR-587 has been documented in the study of Zhang et al ., which demonstrated that inhibition of miR-587 could restore the 5-fluorouracil-induced cell apoptosis in colorectal cancer and even cause significant declines in drug resistance [ 11 ]. Largely in agreement with our present findings, upregulation of miR-587 has been identified in cervical cancer and specific inhibitor-induced miR-587 knockdown exerts inhibitory effects on tumor growth [ 21 ]. The rescue experiments in this study unearthed that miR-587 upregulation-induced by mimics could reverse the suppressed cell proliferation and colony formation triggered by PGM5-AS1 overexpression.…”

Decreased interferon regulatory factor 6 expression due to DNA hypermethylation predicts an unfavorable prognosis in clear cell renal cell carcinoma

“…For instance, IRF8 functions as a tumor suppressor in RCC, and its mediated interferon signal pathway is involved in the pathogenesis of RCC [23]; RCC patients with high IRF8 expression level have prolonged OS compared to patients with low level of IRF8 expression [24]; IRF1 plays a pivotal role in the interferon-gamma-mediated-enhancement of Fas/ CD95-mediated RCC cells apoptosis [25]. Although previous studies have indicated that IRF6 also plays important roles in multiple tumors, including gastric cancer [13], nasopharyngeal carcinoma [14], squamous cell carcinoma [15] and cervical cancer [16], the expression pattern and prognostic value of IRF6 in ccRCC are still uncertain.…”

“…Recent studies have shown that IRF6, as a member of the IRFs family, plays an important role in the occurrence and development of a variety of tumors. For example, IRF6 predicts a favorable prognosis in gastric cancer [13]; IRF6 distinctively reverses stemness phenotype in nasopharyngeal carcinoma [14]; IRF6 downregulation promotes squamous cell carcinoma (SCC) cell invasive and reintroduction of IRF6 into SCC cells inhibits cell growth [15]; miR-587 promotes cervical cancer by repressing IRF6 [16]. However, the expression pattern and clinicopathological role of IRF6 and its prognostic value in ccRCC remain unclear.…”

CRISPR Screening of E3 Ubiquitin Ligases Reveals Ring Finger Protein 185 as a Novel Tumor Suppressor in Glioblastoma Repressed by Promoter Hypermethylation and miR-587

“…6B). As miR-525 was shown to repress glioma cells proliferation in other studies [42], we chose miR-587 for subsequent analysis, for its oncogenic role in multiple cancer types [43][44][45] except glioma. So, we rst studied the function of miR-587 in glioma cells with CCK8, apoptosis and wound healing assays.…”