scholarly journals Estrogen Receptor Variant ER-α36 Facilitates Estrogen Signaling via EGFR Signaling in Glioblastoma

2021 ◽  
Author(s):  
Chao Qu ◽  
Cui Wang ◽  
Hongyan Li ◽  
Chao Han ◽  
Ying Li ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Western Blot ◽  
Estrogen Receptors ◽  
Cell Lines ◽  
Malignant Tumors ◽  
Mapk Pathway ◽  
Cell Counting ◽  
Estrogen Signaling ◽  
Glioblastoma Cell ◽  
Cell Cycle Protein

Abstract Background: Glioblastoma (GBM) is a deadly and common primary brain tumor. Poor prognosis is linked to high proliferation and cell heterogenity. Sex differences may play a role in patient outcome. Previous studies showed that ER-α36, a variant of the estrogen receptor, mediated non-genomic estrogen signaling and is highly expressed in many estrogen receptors (ER)-negative malignant tumors. ER-α36 also associates with the epidermal growth factor receptor (EGFR).Aim: The primary purpose of this study is to investigate the cross-talk between ER-α36 and EGFR in estrogen (E2) induced glioblastoma cell proliferation.Methods: The expression of estrogen receptors were tested by immunofluorescence in the specimens. The expression of ER-α36, EGFR and cell cycle protein were measured by qPCR and Western blot. The numbers of cells were tested through cell counting, and cell signaling pathway activation also determined by Western blot.Results: Here, we showed that ER-α36 was highly expressed and confirmed that ER-α36 co-labels with EGFR in human glioma specimens using immunohistochemical techniques. We also investigated the mechanisms of estrogen induced proliferation in ER-a-negative cell lines U87 and U251. We found that glioblastoma cell lines U87 and U251 showed varying responsive to mitogenic estrogen signaling which correlated with ER-α36 expression, and knockdown of ER-α36 diminished the response. Exposure to estrogen also caused up-regulation of cyclin protein expression in vitro. We also found that low concentrations of estrogen promoted SRC-Y-416 and inhibited SRC-Y-527 phosphorylation, corresponding with activated SRC signaling. Inhibiting SRC or EGFR abolished estrogen-induced mitogenic signaling, including cyclin expression and MAPK phosphorylation.Conclusion: Cumulatively, our results demonstrate that ER-α36 promotes non-genomic estrogen signaling via the EGFR/SRC/MAPK pathway in glioblastoma. This may be important for the treatment of ER-a-negative glioblastomas that retain high level of ER-α36, since estrogen may be a viable therapeutic target for these patients.

scholarly journals miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled-Related Protein-1 in Cholangiocarcinoma

2018 ◽  
Vol 49 (5) ◽  
pp. 1933-1942 ◽  
Author(s):  
Peng-Cheng Kang ◽  
Kai-Ming Leng ◽  
Yue-Ping Liu ◽  
Yang Liu ◽  
Yi Xu ◽  
...  
Keyword(s):  
Western Blot ◽  
Cell Lines ◽  
Colony Formation ◽  
Malignant Tumors ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Related Protein ◽  
Qrt Pcr ◽  
Induced Apoptosis

Background/Aims: Cholangiocarcinoma (CCA) is one of the most common malignant tumors of the biliary tract originating from biliary epithelial cells. Although many therapeutic strategies have been developed to treat CCA, the survival rate for CCA patients is still quite low. Thus it is urgent to elucidate the pathogenesis of CCA and to explore novel therapeutic targets. miR-191 has been shown to be associated with many human solid cancers, but the function of miR-191 in CCA is still poorly understood. Methods: We first investigated the expression level of miR-191 in human CCA tissues and cell lines with quantitative real-time PCR (qRT-PCR). The effects of miR-191 on CCA cells were determined by Cell Counting Kit-8 assay, colony formation assay and acridine orange/ethidium bromide staining. Finally, we utilized qRT-PCR, western blot and luciferase reporter assays to verify the miR-191 target gene. Results: We showed that miR-191 was up-regulated in CCA cell lines and patients. Knockdown of miR-191 by transfection of its inhibitor sequence blocked RBE cells viability and induced apoptosis of RBE cells. Both qRT-PCR and western blot analysis showed that the secreted frizzled-related protein-1 (sFRP1) level was negatively correlated with that of miR-191. Luciferase assay validated that sFRP1 was a direct target of miR-191. Moreover, knockdown of miR-191 led to suppression of Wnt/β-catenin signaling activation. Co-transfection of sFRP1 small interfering RNA (siRNA) and miR-191 inhibitor re-activated the Wnt/β-catenin signaling pathway as detected by an increased level of β-catenin and phosphorylation of GSK-3β, and restored the expression of survivin and c-myc in RBE cells. Co-transfection of sFRP1 siRNA with miR-191 inhibitor restored the colony formation ability and viability of RBE cells. Conclusion: Taken together, our results demonstrate a novel insight into miR-191 biological function in CCA. Our findings suggest that miR-191 is a potential therapeutic target of CCA treatment.

Membrane-Initiated Estradiol Signaling in the Central Nervous System

2019 ◽  
Author(s):  
Paul E. Micevych ◽  
Melinda A. Mittelman-Smith
Keyword(s):  
Nervous System ◽  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
G Protein ◽  
Nuclear Receptors ◽  
Signaling Cascades ◽  
Estrogen Signaling ◽  
Female Reproduction ◽  
Brain Physiology ◽  
The Brain

In the last two decades of the 20th century, key findings in the field of estrogen signaling completely changed our understanding of hormones: first, steroidogenesis was demonstrated in the CNS; second, a vast majority of cells in the nervous system were shown to have estrogen receptors; third, a second nuclear estrogen receptor (ERß) was cloned; and finally, “nuclear” receptors were shown to be present and functional in the cell membrane. Shortly thereafter, even more membrane estrogen receptors were discovered. Steroids (estrogens, in particular) began to be considered as neurotransmitters and their receptors were tethered to G protein-coupled receptor signaling cascades. In some parts of the brain, levels of steroids appeared to be independent of those found in the circulation and yet, circulating steroids had profound actions on the brain physiology. In this review, we discuss the interaction of peripheral and central estrogen action in the context of female reproduction—one of the best-studied aspects of steroid action. In addition to reviewing the evidence for steroidogenesis in the hypothalamus, we review membrane-localized nuclear receptors coupling to G protein-signaling cascades and the downstream physiological consequences for reproduction. We will also introduce newer work that demonstrates cell signaling for a common splice variant of estrogen receptor-α (ERα), and membrane action of neuroprogesterone in regulating estrogen positive feedback.

Interactions Between BAFF and BAFF Receptors Are Involved in Macrophage-Induced Bortezomib Resistance in Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4429-4429
Author(s):  
Jing Chen ◽  
Donghua He ◽  
Xing Guo ◽  
Qingxiao Chen ◽  
Xuanru Lin ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Drug Resistance ◽  
Western Blot ◽  
B Cell ◽  
Cell Lines ◽  
Conflicts Of Interest ◽  
Cell Counting ◽  
Therapeutic Modality ◽  
Second Primary ◽  
Induced Apoptosis

Abstract Background:B-cell-activating factor (BAFF) is a member of the TNF family that critical for maintenance of B-cell development and homeostasis. BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA) and transmembrane activator and CAML interactor (TACI) are three BAFF receptors. It has been reported that BAFF is expressed by neutrophils, monocytes, dentritic cells and macrophages and modulates the proliferation, survival and drug resistance of multiple myeloma (MM) cells. Our previous study showed that, macrophages protect MM cells from drug-induced apoptosis by direct interaction with MM cells. We hypothesized that BAFF/BAFF receptors play a role in macrophage-induced bortezomib resistance in myeloma. Methods: First, the expression levels of BAFF and its three receptors in primary MM cells, MM cell lines and peripheral blood monocyte(PBMC)-induced macrophages were detected by semiquantitative real time-polymerase chain reaction (qPCR),Western blot and flow-cytometry. Also the concentration of BAFF in the supernatants of MM patients' bone marrow, MM cell lines and macrophages were determined by ELISA. Second, Primary MM cells and MM cell lines were cocultured with macrophages for the indicated time (usually 4-6h and 24h), for some experiments, we added bortezomib to the coculture system. Cell viability and apoptosis of MM cells were verified by Cell Counting Kit-8(CCK8) after treated with recombinant human (rh) BAFF, BAFF neutralizing antibody and BAFF siRNA. The interactions between BAFF and its receptors are unveiled by flow-cytometry. Then, cell survival signaling activations that may confer MM drug resistance were examined by Western blot. Results: Two receptors of BAFF, TACI and BCMA were highly expressed in various MM cell lines. The expressions of BAFF in PBMC-induced macrophages were heterogeneous. Functional studies showed that rhBAFF promoted RPMI8226 and ARP1 myeloma cells growth (P<0.05) and protected them from bortezomib-induced apoptosis (P<0.05). Then we verified macrophage-mediated MM drug resistance by directly coculturing MM cells (ARP-1, RPMI8226) with PBMC-derived macrophages from healthy donors. The macrophage-induced bortezomib resistance was attenuated by neutralizing antibodies(P<0.05) and siRNA of BAFF(P<0.01) . Next we found that in MM cells cocultured with macrophages, bortezomib-induced PARP and caspase-3 cleavages were highly repressed and phosphorylated Src ,AKT and Erk1/2 were upregulated which indicated that BAFF-mediated MM drug resistance may be through ERK1/2 and Src pathway .In addition, BAFF induced activation of NF-κB2,a pathway critical for the growth and survival of these cells. Conclusions: Our data show that macrophage might induce drug resistance of MM cells by the interaction of BAFF and BAFF receptors, leading to a reduction in caspase proteins and subsequent activation of Src and Erk1/2 kinases and NF-κB2 pathways .These studies reveal a promising unknown role for BAFF/BAFF receptors, suggesting that targeting macrophage-MM interactions may represent a promising therapeutic modality. Disclosures No relevant conflicts of interest to declare.

scholarly journals Anticancer Effect of Natural Product Sulforaphane by Targeting MAPK Signal through miRNA-1247-3p in Human Cervical Cancer Cells

2020 ◽  
Vol 11 (1) ◽  
pp. 7943-7972
Keyword(s):  
Cervical Cancer ◽  
Flow Cytometry ◽  
Western Blot ◽  
Hela Cells ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Cell Counting ◽  
Hela Cell Lines ◽  
Cervical Cancer Cells ◽  
Induced Apoptosis

The prognosis of cervical cancer remains poor. Sulforaphane, an active ingredient from cruciferous plants, has been identified as a potential anticancer agent in various cancers. However, there is little information about its effect on cervical cancer. Here, we conducted a present study to uncover the effect and the potential mechanisms of sulforaphane on cervical cancer. HeLa cells were treated with sulforaphane, and cell proliferation and apoptosis were assessed by Cell Counting Kit-8, Western blot, flow cytometry, and immunofluorescence. Then, next-generation sequencing (NGS) and bioinformatics tools were used to analyze mRNA-seq, miRNA-seq, and potential pathways. Finally, qRT-PCR, Cell Counting Kit-8, flow cytometry, small RNAs analysis, and Western blot were performed to evaluate the biological function of miR1247-3p and MAPK pathway in HeLa cell lines. Sulforaphane significantly suppressed the viability and induced apoptosis of HeLa cells. NGS and bioinformatics analysis showed sulforaphane exerted its anti-tumor activities through miR1247-3p and the MAPK signaling pathway. Further analysis suggested that sulforaphane could activate MAPK pathway via down-regulating the expression of miR-1247-3p. Sulforaphane inhibited proliferation and promoted apoptosis of HeLa cells via down-regulation of miR-1247-3p and activating the MAPK pathway. These findings provide preliminary experimental evidence for the treatment of cervical cancer with sulforaphane.

scholarly journals miR-489 confines uncontrolled estrogen signaling through a negative feedback mechanism and regulates tamoxifen resistance in breast cancer

2020 ◽  
Author(s):  
Mithil Soni ◽  
Ozge Saatci ◽  
Yogin Patel ◽  
Manikanda Raja Keerthi Raja ◽  
Xinfeng Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Lines ◽  
Tamoxifen Resistance ◽  
Resistant Cell ◽  
Estrogen Signaling ◽  
Breast Cancers ◽  
Tamoxifen Resistant ◽  
Hormonal Therapies

Abstract Background Approximately 75% of diagnosed breast cancer tumors are Estrogen receptor (ER) positive tumors and are associated with better prognosis due to their response to hormonal therapies. However, around 40% of patients relapse after hormonal therapies. In the current study, we aimed to evaluate miR-489 as a novel molecular target to combat tamoxifen resistance.Methods Genomic analysis of gene expression profiles in primary breast cancers and tamoxifen resistant cell lines unveiled the potential role of miR-489 in regulation of estrogen signaling and development of tamoxifen resistance. We manipulated miR-489 expression in breast cancer cell lines by transient transfection of miR-489 mimic or establishment of knockout cell lines using the CRISPR/Cas9 system to study the reciprocal regulation of miR-489 and estrogen/ER signaling pathways. Cell proliferation, tumor sphere formation assay and flow cytometry analysis were conducted to investigate the role of miR-489 on estrogen-induced cell proliferation, cancer stem cells expansion and development of tamoxifen resistance.Results miR-489 expression was significantly downregulated in tamoxifen-resistant cell lines. Low levels of miR-489 were associated with poor clinical outcomes in patients with hormone treatment. In vitro analysis showed that loss of miR-489 expression promoted tamoxifen resistance while overexpression of miR-489 in tamoxifen-resistant cells restored tamoxifen sensitivity. Mechanistically, we found that miR-489 is an estrogen regulated miRNA that negatively regulated estrogen receptor signaling by using at least the following two mechanisms: i) modulation of ER phosphorylation status by inhibiting MAPK and AKT kinase activities; ii) regulation of nucleus to cytosol translocation of estrogen receptor α (ERα) by decreasing p38 expression and consequently ER phosphorylation. In addition, miR-489 could break the positive feed-forward loop between estrogen-ERα axis and p38 MAPK in breast cancer cells which was necessary for its function as transcription factor.Conclusion Our study unveiled the underlying molecular mechanism by which miR-489 regulates estrogen signaling pathway through a negative feedback loop and uncovered its role in the development of and overcoming tamoxifen resistance in breast cancers.

scholarly journals Sex- and Age-Related Estrogen Signaling Alteration in Inflammatory Bowel Diseases: Modulatory Role of Estrogen Receptors

2019 ◽  
Vol 20 (13) ◽  
pp. 3175 ◽  
Author(s):  
Damian Jacenik ◽  
Adam I. Cygankiewicz ◽  
Anna Mokrowiecka ◽  
Ewa Małecka-Panas ◽  
Jakub Fichna ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
Inflammatory Bowel Diseases ◽  
Protein Level ◽  
Estrogen Signaling ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Age Related ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The pathogenesis of inflammatory bowel diseases (IBD) seems to be associated with alterations of immunoregulation. Several lines of evidence suggest that estrogens play a role in the modulation of immune responses and may be related to the etiology of IBD. The purpose of this work was to examine the involvement of G protein-coupled estrogen receptor (GPER), estrogen receptor α (ERα), estrogen receptor β (ERβ) and ERα spliced variants ERα36 and ERα46 in Crohn’s disease (CD) and ulcerative colitis (UC). The studied group included 73 patients with IBD and 31 sex and age-related controls. No differences in serum levels of 17β-estradiol nor of CYP1A1 and SULT1E1 enzymes involved in estrogen catabolism were stated. The expression pattern of estrogen receptors in tissue samples was quantified using real-time PCR and Western blotting. Statistically significant up-regulation of GPER and ERα in both CD and UC as well as down-regulation of ERβ in CD patients was found. However, differences in the expression of estrogen receptors in CD and UC have been identified, depending on the sex and age of patients. In men, up-regulation of GPER, ERα and ERα46 expression was shown in CD and UC patients. In women under 50 years of age, GPER protein level increased in UC whereas ERβ expression tended to decrease in CD and UC patients. In turn, in women over 50 the protein level of ERα increased in UC while ERβ expression decreased in CD patients. Dysregulation of estrogen receptors in the intestinal mucosa of patients with CD and UC indicates that estrogen signaling may play a role in the local immune response and maintain epithelial homeostasis in a gender- and age-dependent manner.

Increased expression of estrogen-related receptor a (ERRa) is a negative prognostic predictor in human prostate cancer

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Prostate Cancer ◽  
Western Blot ◽  
Cell Lines ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Human Prostate ◽  
Estrogen Signaling ◽  
Significant Prognostic Factor ◽  
Cancerous Lesions ◽  
Estrogen Related Receptor

The nuclear receptor ERRa (estrogen-related receptor a) isknown to modulate the estrogen-signaling pathway, but the biologicalsignificance of ERRa in the prostate remains unclear. Weinvestigated the expression of ERRa in human prostate tissuesand cancer cell lines to evaluate the potential roles of the receptorin prostate cancer (PC). Western blot analysis of ERRa was performedin three cell lines of human PC (LNCaP, DU145 and PC-3). The expressions of ERRa in cancerous lesions (n 5 106) andbenign foci (n 5 99) of 106 surgically obtained prostate specimenswere evaluated by immunohistochemistry. The relationshipsbetween the ERRa expression and clinicopathological featureswere evaluated. Western blot analysis using the polyclonal anti-ERRa antibody detected a 52 kD band in all three PC cell lines.Positive immunostaining of ERRa in the nuclei was found in 73(69%) cancerous and 47 (47.5%) benign epithelium, whereas thestromal tissues were negative for ERRa. The mean immunoreactivityscore (IR score) of the cancerous lesions (3.5 6 2.6) was significantlyhigher than that of the benign foci (1.8 6 2.1) (p &lt;0.0001). The IR score of the cancerous lesions significantly correlatedwith the Gleason score (p 5 0.0135). Univariate and multivariatehazard analyses revealed significant correlations betweenelevated ERRa expression and poor cancer-specific survival (p 50.0141 and 0.0367, respectively). The enhanced expression ofERRa might play a role in the development of human PC andserve as a significant prognostic factor for the disease.' 2007 Wiley-Liss, Inc.

Paradoxical cross-talk between the Stat3 and MAPK pathways in CCL25-CCR9 mediated pancreatic cancer growth and proliferation.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 231-231
Author(s):  
Maithao N. Le ◽  
Xiaoming Shen ◽  
Wendy Lee ◽  
Marjun Philip Duldulao ◽  
Julio Garcia-Aguilar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Western Blot ◽  
Cell Lines ◽  
Pancreatic Cancer Cell ◽  
Mapk Pathway ◽  
Western Blot Assay ◽  
Mapk Pathways ◽  
Stat3 Signaling ◽  
Pancreatic Cancer Cells

231 Background: Chemokine receptors have been shown to regulate the progression of several malignancies. Signal transducer and activator of transcription 3 (Stat3) may contribute to the invasive phenotype of several human cancers, but its upstream signals have not been well characterized. Our objective was to investigate the relationship between the CCL25-CCR9 axis and Stat3 signaling in pancreatic cancer cells. Methods: We exposed two established human pancreatic cancer cell lines PANC-1 and MIAPaCa-2 to the cytokine CCL25 (800 ug/uL for 20 min) and measured the activation of Stat3 (phosho-Stat3) by Western blot assay. Stattic, a small molecule Stat3 inhibitor, was used (20uM) to antagonize Stat3 signaling. We also measured activation level of extracellular signal-regulated kinase (phospho-ERK) following CCL25 exposure and used UO126 (10uM), a small molecule MEK inhibitor, to antagonize the MAPK pathway. Changes in cell proliferation were measured by CellTiter Glo Fluorescence assay. Results: Constitutive phosphorylation of Stat3 was observed in both pancreatic cancer cell lines. Exposure of MIAPaCa-2 to CCL25 further increased phospho-Stat3 levels on Western blot assay. We also observed a concomitant increase in phospho-ERK levels with exposure to CCL25 in both cell lines. Exposure of pancreatic cancer cells to CCL25 significantly increased cell proliferation. To determine the mechanism of CCR9-mediated cell proliferation, we used stattic and UO126 to specifically inhibit Stat3 and MEK activation, respectively. Interestingly, pre-treatment with stattic prior to CCL25 exposure resulted in a paradoxical enhancement of phospho-ERK levels. Conversely, inhibition of the MAPK pathway with UO126 led to a paradoxical enhancement of phospho-Stat3 levels. Conclusions: Our results demonstrate that CCL25 activates Stat3 and MAPK pathways to contribute to pancreatic cancer proliferation. We also show potential cross-talk between Stat3 and MAPK pathways, wherein antagonism of one pathway resulted in paradoxical activation of the other pathway. Our findings suggest that therapeutic targeting of downstream pathways may require a multi-drug approach.

scholarly journals miR-27b Targets HOXB8 to Inhibit Malignant Behaviors of Osteosarcoma

2019 ◽  
Vol 18 ◽  
pp. 153303381987079
Author(s):  
Yingyong Wu ◽  
Jinyun Peng
Keyword(s):  
Cell Proliferation ◽  
Western Blot ◽  
Cell Lines ◽  
Colony Formation ◽  
Cell Counting ◽  
Osteosarcoma Cell ◽  
Polymerase Chain ◽  
And Migration ◽  
Insight Into

MicroRNAs function as either tumor suppressor or oncogene in human cancers. This study aimed to explore the role of miR-27b in osteosarcoma. Expression of miR-27b or homeobox B8 in osteosarcoma cell lines was analyzed by quantitative real-time polymerase chain reaction and Western blot, respectively. Luciferase activity reporter assay and Western blot were conducted to explore the association between miR-27b and homeobox B8. Cell Counting Kit-8, colony formation assay, and wound-healing assay were performed to investigate the role of miR-27b or homeobox B8 on cell proliferation, colony formation, and cell migration. Expression of miR-27b was significantly reduced, while homeobox B8 was increased in osteosarcoma cell lines. In addition, homeobox B8 was validated as a direct target of homeobox B8. Moreover, miR-27b regulates osteosarcoma cell proliferation, colony formation, and migration through targeting homeobox B8. Taken together, our study provides novel insight into the progression of osteosarcoma, and the miR-27b–homeobox B8 axis identified may be developed as therapeutic targets against hepatocellular carcinoma in the future.

scholarly journals MicroRNA-505-5p functions as a tumor suppressor by targeting cyclin-dependent kinase 5 in cervical cancer

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Elena Kapora ◽  
Shujun Feng ◽  
Wei Liu ◽  
Indira Sakhautdinova ◽  
Bo Gao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Western Blot ◽  
Cell Lines ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Cyclin Dependent Kinase ◽  
Mesenchymal Transition ◽  
Cyclin Dependent Kinase 5

Abstract MicroRNAs (miRs) are considered to be tumor suppressors or oncogenes as they regulate cell proliferation, migration, invasion, and differentiation. Recently, microRNA-505 (miR-505) has been reported as being involved in the progression of several human cancers. In the present study, we aim to investigate the expression rate and functional role of miR-505-5p in cervical cancer (CC) to determine its significance regarding the disease’s development. The expression of miR-505-5p and cyclin-dependent kinase 5 (CDK5) in specimens of patients with CC and CC cell lines was examined by quantitative real-time PCR (qRT-PCR) and Western Blot. The relationship between miR-505-5p and CDK5 was verified by luciferase reporter assay. Cell counting kit-8 (CCK-8) assay, Scratch wound healing assay and transwell assay were used to detect the roles of miR-505-5p and CDK5 in CC cell functions. Western Blot was utilized to explore the epithelial–mesenchymal transition (EMT) markers. The result showed that in CC tissues and CC cell lines miR-505-5p was down-regulated while CDK5 level was up-regulated. MiR-505-5p was closely correlated with the metastasis-associated clinicopathological features. Overexpression of miR-505-5p inhibited cell viability, cell metastasis and EMT in CC cells. CDK5 was confirmed as a direct target of miR-505-5p and inverse relationship between them was also observed. Overexpression of CDK5 reduces the inhibitory effects of miR-505-5p in CC. Taken together, these results determine that miR-505-5p is a tumor suppressor miRNA which regulates tumor cell proliferation, migration, and invasion via binding to the functional target CDK5 and demonstrates its potential for future use in the treatment of CC.

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