scholarly journals Knockdown of Circular RNA hsa_circ_PVT1 Inhibited Laryngeal Cancer Progression via Preventing wnt4/β-Catenin Signaling Pathway Activation

2021 ◽  
Vol 9 ◽  
Author(s):  
Feng Yu ◽  
Ying Lin ◽  
Mao-Mao Ai ◽  
Guo-Jie Tan ◽  
Jia-Li Huang ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Laryngeal Cancer ◽  
Mrna Level ◽  
Circular Rna ◽  
Signal Pathway ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Pathway Activation ◽  
The Relationship ◽  
Apoptosis Level

AimTo explore the function and mechanism of circular has_circ_PVT1 on laryngeal cancer (LC).MethodsMicroarray chip was performed to screen the differential expression of circRNA. Western blot and qRT-PCR was employed to detect the protein and mRNA level. CCK-8, clone formation, cell cycle, wound healing, and Transwell assay were performed to detect the cell proliferation, migration, and invasion ability. Luciferase assay and Fish were used to confirm the relationship between circ_PVT1/CBX4 and miR-21-5p. Flow cytometry and TUNEL assay were carried out to assess the apoptosis level.ResultsThe upregulation of circ_PVT1 was found in LC tissues and cells. Silencing of circ_PVT1 inhibited LC progression via targeting miR-21-5p and indirectly controlling CBX4. Wnt4/β-catenin signal pathway was inactivated by inhibiting the expression of circ_PVT1.ConclusionKnockdown of circ_PVT1 prevented LC progression via targeting miR-21-5p/CBX4 by inhibiting wnt4/β-catenin signal pathway, which could provide a novel therapeutic target for LC.

scholarly journals Decreased level of miR-1301 promotes colorectal cancer progression via activation of STAT3 pathway

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Fangfang Yang ◽  
Hua Wang ◽  
Bianbian Yan ◽  
Tong Li ◽  
Lulu Min ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Progression ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Aberrant Expression ◽  
Cell Migration And Invasion ◽  
Lovo Cells ◽  
Colorectal Cancer Progression

Abstract The molecular pathogenesis of colorectal cancer (CRC) has been widely investigated in recent years. Accumulating evidence has indicated that microRNA (miRNA) dysregulation participates in the processes of driving CRC initiation and progression. Aberrant expression of miR-1301 has been found in various tumor types. However, its role in CRC remains to be elucidated. In the present study, we identified miR-1301 was enriched in normal colorectal tissues and significantly down-regulated in CRC. Decreased level of miR-1301 strongly correlated with aggressive pathological characteristics, including advanced stage and metastasis. Bioinformatics and dual luciferase assay demonstrated that STAT3 is a direct target of miR-1301. Gain and loss-of-function assays showed that miR-1301 had no effect on cell proliferation. Overexpression of miR-1301 suppressed cell migration and invasion capacity of pSTA3-positive LoVo cells, but not pSTAT3-negative SW480 cells, while inhibition of miR-1301 consistently promoted cell migration and invasion in both cell lines. Additionally, miR-1301 inhibition restored the suppressed migration and invasion of STAT3- knockdown LoVo cells. MiR-1301 functioned as a tumor suppressor to modulate the IL6/STAT3 signaling pathway. In summary, this study highlights the significant role of miR- 1301/STAT3 axis in CRC metastasis.

Circular RNA circVAPA regulates breast cancer cell migration and invasion via sponging miR-130a-5p

Epigenomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 303-317 ◽  
Author(s):  
Si-ying Zhou ◽  
Wei Chen ◽  
Su-jin Yang ◽  
Jian Li ◽  
Jun-ying Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Mirna Sponge ◽  
Cell Migration And Invasion ◽  
Cancer Migration ◽  
Cancer Tissues ◽  
The Relationship

Aim: We aimed to explore the roles of circular RNA, circVAPA in regulating cell migration and invasion of breast cancer. Materials & methods: CircVAPA expression was detected in breast cancer tissues and cells. The role of circVAPA was evaluated by MTT assay, wound-healing and transwell assay. The relationship between circVAPA and miR-130a-5p and the location of circVAPA were explored. Results: We discovered that circVAPA was dysregulated in breast cancer tissues and cells. Ectopic circVAPA regulated breast cancer migration, invasion and proliferation. CircVAPA was mainly expressed in the cytoplasm and could act as a miRNA sponge for miR-130a-5p, but did not regulate its parental gene. Conclusion: CircVAPA may promote migration and invasion capacity of breast cancer via harboring miR-130a-5p.

miR-938 Promotes the Proliferation and Invasion of Prostate Cancer Through Targeting Pleckstrin Homology (PH) Domain Leucine-Rich-Repeats Protein Phosphatase 2 and Forkhead Box O3

2019 ◽  
Vol 9 (5) ◽  
pp. 583-591
Author(s):  
Xin Deng ◽  
Fengye Wang ◽  
Qianjin Zhang ◽  
Xuejian Yang ◽  
Hao Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Phosphatase ◽  
Mrna Level ◽  
Signal Pathway ◽  
Migration And Invasion ◽  
Ph Domain ◽  
Pleckstrin Homology ◽  
Forkhead Box ◽  
Protein Phosphatase 2 ◽  
Leucine Rich Repeats

miR-938 is generally reported to be up-regulated in various cancers, which affect the tumor progression. In the present study, we investigated the biological role and underlying mechanisms of miR-938 in prostate cancer (PCa). PCa is the most common malignant tumor in males with markedly increasing incidence in recent years. Up-regulation of miR-938 occurred in PCa tissues and cell lines at mRNA level. Functional assays were established to demonstrate that miR-938 mimics significantly promoted the proliferation, migration and invasion of PCa cells, while knockdown of miR-938 led to the inhibition. Luciferase activity assay suggested miR-938 directly bound to the 3 UTR of PHLPP2 (Pleckstrin Homology (PH) domain Leucine-rich-repeats Protein Phosphatase 2) and FOXO3 (Forkhead box O3). Our results also showed that the regulation activity of miR-938 on progression of PCa was partially through its negative regulation on PHLPP2 and FOXO3. Our results deciphered the mechanism through which miR-938 promoted the progression of PCa by activation of PI3K/AKT signal pathway. Together, inactivation of PI3K/AKT signal pathway through down-regulation of miR-938 could be an important mechanism in inhibiting PCa progression, thus shedding light on the development of novel anti-tumor therapies for treatment of PCa.

scholarly journals Circ-ZFR Promotes Progression of Bladder Cancer by Upregulating WNT5A Via Sponging miR-545 and miR-1270

2021 ◽  
Vol 10 ◽  
Author(s):  
Liping Luo ◽  
Pingping Miao ◽  
Yao Ming ◽  
Jie Tao ◽  
Hongchun Shen
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Pearson Correlation ◽  
Survival Rates ◽  
Circular Rna ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Novel Target

BackgroundBladder cancer is one of the most common cancers all over the world. CircZFR is a circular RNA and has been implicated in tumor generation and invasion. However, the exact role of circZFR in the development of bladder cancer (BCa) remains unknown. This study aimed to investigate the function of circZFR in BCa, and further to probe into the association between circ-ZFR, miR-545/miR-1270 and WNT5A.MethodsThe expression of circZFR in BCa was quantified by qRT-PCR and was positively correlated with the prognosis of BCa patients. Next, the stable knockdown of circZFR BCa cell lines was established and the resulting capacities of proliferation, migration and invasion were measured. The association of circZFR with miR-1270/miR-545 was predicted by circinteractome prediction, and was confirmed by luciferase assay as well as RNA pull down assay. Furthermore, miRNA inhibitors, WNT5A overexpression and Pearson correlation analysis were used to examine the relationship between circZFR, miR-1270/miR-545 and WNT5A.ResultsThe expression of CircZFR was up-regulated both in BCa tissues and in BCa cell lines, and was positively correlated with patient survival rates. Blocking of circZFR’s expression by RNA inhibitors suppressed the proliferation, migration and invasion of BCa cells both in vitro and in vivo. On the other hand, overexpression of target miRNA supported that circZFR directly interact with miR-545 and miR-1270. Moreover, we demonstrated that circZFR promotes the progression of BCa by upregulating WNT5A’s expression via sponging miR-545 and miR-1270.ConclusionsCircZFR promotes the proliferation, migration and invasion of BCa cells by upregulating WNT5A signaling pathway via sponging miR-545 and miR-1270. These results provide new insights into the molecular mechanism of circZFR in BCa progression, and more important, a novel target for BCa clinical treatment.

scholarly journals Circular RNA circANKS1B as the Sponge of miR-152-3p Promotes Prostate Cancer Progression by up-Regulating TGF-α Expression

2020 ◽  
Author(s):  
Liangjun Tao ◽  
Xinyuan Pan ◽  
Jiawei Wang ◽  
Li Zhang ◽  
Lingsong Tao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Prostate Cancer Progression ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
And Function ◽  
The Impact

Abstract Background: Growing studies indicate that circRNAs play critical roles in human diseases, and show great potential as biomarkers and therapeutic targets. This study aims to investigate the expression and function of circANKS1B in prostate cancer (PC).Methods: The expression of circANKS1B and miRNA-152-3p were determined by real-time qRT-PCR. The cell migration and invasion were measured by transwell assay. The interaction between circANKS1B and miR-152-3p was confirmed by dual-luciferase reporter gene assay. Rescue experiments were conducted to demonstrate whether circANKS1B regulated the migration and invasion of PC cells by the circANKS1B-miR-152-3p-TGF-α pathway.Results: The expression of circANKS1B was dramatically up-regulated both in PC cells and tissues. Moreover, high circANKS1B expression was associated with a poor prognosis of PC patients. Dual-luciferase reporter assay indicated that circABKS1B directly bound to miRNA-152-3p. Furthermore, circANKS1B negatively regulated miR-152-3p expression. Knockdown of circANKS1B remarkably suppressed PC cells invasion and TGF-α expression, while the effects of circANKS1B silencing were reversed by miR-152-3p deficiency. In addition, the impact of miR-152-3p silencing on PC cell invasion was also abrogated by TGF-α deficiency. In all, circANKS1B as the sponge of miR-152-3p promotes prostate cancer progression by up-regulating TGF-α expression.Conclusion: Our findings reveal that circANKS1B could be a potential prognostic biomarker and therapeutic target of PC.

scholarly journals SSRP1 Promotes Lung Cancer Progression by Blocking the WNT Pathway and is Negatively Regulated by miRNA-28-5p

2021 ◽  
Author(s):  
Shengnan Jia ◽  
Qian Wang ◽  
Yan Jiao ◽  
Baofeng Guo ◽  
Lihui Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Wnt Pathway ◽  
Human Lung Cancer ◽  
Migration And Invasion ◽  
Lung Cancer Cell ◽  
Over Expression ◽  
The Relationship

Abstract Background: Structure-specific recognition protein 1 (SSRP1) plays important roles in the development of various tumors. Numerous reports have described the effects of microRNAs (miRNAs) on lung cancer apoptosis, metastasis and proliferation. However, the relationship between SSRP1 and miRNAs in the development of lung cancer remains unclear. Therefore, the purpose of our study was to explore the functions of SSRP1 in the occurrence and development of lung cancer. Methods: First, we analyzed the expression of SSRP1 in human lung cancer tissues and normal tissues, and the relationship between SSRP1 gene expression and overall survival through the UALCAN and GEPIA browsers. Second, we conducted experiments in vivo and vitro to demonstrate the roles and mechanisms of SSRP1 in the occurrence and development of lung cancer and its relationship with miR-28-5p. Results: Our study demonstrated over-expression of SSRP1 in tissue sections from patients with lung cancer and in lung cancer cell lines, as validated by bioinformatics analysis. The over-expression of SSRP1 was found to be associated with lung cancer development and low overall survival rates. Silencing of SSRP1 by siRNA inhibited lung cancer proliferation, migration and invasion by blocking the WNT signaling pathway in vitro and vivo. We also verified SSRP1 was negatively regulated by miR-28-5p，as predicted by a variety of miRNA-related databases. Further studies showed that miR-28-5p mediated suppression of SSRP1 inhibited lung cancer cell proliferation. Conclusion: Therefore, our data suggested that SSRP1 promotes lung cancer progression by blocking the WNT pathway and is negatively regulated by miRNA-28-5p.

scholarly journals Hypoxia-Related Gene FUT11 Promoted Pancreatic Cancer Progression Via Maintaining The Stabilization of PDK1

2021 ◽  
Author(s):  
Wenpeng Cao ◽  
Zhirui Zeng ◽  
Runsang Pan ◽  
Zhiwei He ◽  
Hao Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Western Blot ◽  
Cancer Progression ◽  
Pyruvate Dehydrogenase Kinase ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Migration And Invasion

Abstract Background: Hypoxia participated in the occurrence and development of pancreatic cancer (PC). However, genes associated with hypoxia respond and their regulated mechanism in PC cells were unclear. The current research was aimed to illuminate the role and hypoxia regulated mechanism of fucosyltransferase 11 (FUT11) in the progression of PC.Methods: After predicting FUT11 as a key hypoxia associated gene in PC using bioinformatics analysis. The expression of FUT11 in PC using quantitative real-time fluorescent PCR, western blot and immunohistochemistry. The effects of FUT11 on PC cells proliferation, migration and invasion under normoxia and hypoxia were detected using Cell Counting Kit 8, 5-ethynyl-2’-deoxyuridine assay, colony formation assay and transwell assay. Spleen capsule injected liver metastasis and subcutaneously injected model were performed to confirm the effects of FUT11 in vivo. Furthermore, western blot, luciferase assay and immunoprecipitation were performed to explore the regulated relationship among FUT11, hypoxia-inducible factor 1α (HIF1α) and pyruvate dehydrogenase kinase 1 (PDK1) in PC.Results: FUT11 was markedly increased of PC cells in hypoxia, up-regulated in the PC clinical tissues, and predicted a poor outcome. Inhibition of FUT11 reduced PC cell growth and mobility of PC cells under normoxia and hypoxia conditions in vitro, and growth and mobility in vivo. FUT11 bind with PDK1 and regulated the expression PDK1 under normoxia and hypoxia. FUT11 knockdown significantly increased the degradation rate of PDK1 under hypoxia, while treatment with MG132 can relieve the degradation of PDK1 induced by FUT11 knockdown. Overexpression of PDK1 in PC cells under hypoxia conditions reversed the suppressiv impacts of FUT11 knockdown on PC cell growth and mobility. In addition, HIF1α bound to the enhancer of FUT11 and increased its expression, as well as co-expressing with FUT11 in PC tissues. Furthermore, overexpress of FUT11 partially rescued the suppressiv effects of HIF1α knockdown on PC cell growth and mobility in hypoxia conditions.Conclusion: Our data further implicate that hypoxia-induced FUT11 in PC contributes to proliferation and metastasis by maintaining the stability of PDK1, and suggest FUT11 maybe a novel and effective target for treatment of pancreatic cancer.

scholarly journals MicroRNA-1271-5p inhibits the tumorigenesis of ovarian cancer through targeting E2F5 and negatively regulates the mTOR signaling pathway

2020 ◽  
Author(s):  
Qin Li ◽  
Junyu Shi ◽  
Xiaoli Xu
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Poor Prognosis ◽  
Mtor Signaling ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway ◽  
Direct Target ◽  
The Relationship

Abstract Background: MicroRNA-1271-5p (miR-1271-5p) has been reported to participate in the progression of many human cancers. However, the role of miR-1271-5p still remains unclear in ovarian cancer (OC). Therefore, we explored the effect of miR-1271-5p on the development of OC in present study. Methods: We measured the miR-1271-5p expression via the qRT-PCR assay. Then the function of miR-1271-5p was analyzed through MTT and Transwell assays. The relationship among miR-1271-5p and E2F5 was verified by dual luciferase assay. The protein expression levels were examined through western blot.Results: MiR-1271-5p was downregulated in OC tissues which predicted poor prognosis of OC patients. Moreover, E2F5 was a direct target of miR-1271-5p in OC. And miR-1271-5p suppressed cell proliferation, migration and invasion in OC through targeting E2F5. Furthermore, E2F5 was upregulated in OC tissues which predicted poor prognosis of OC patients. Besides that, miR-1271-5p suppressed EMT and mTOR pathway in OC. Conclusion: MiR-1271-5p inhibited the tumorigenesis of OC through targeting E2F5 and negatively regulated the mTOR signaling pathway.

Circular RNA HIPK3 plays a carcinogenic role in cervical cancer progression via regulating miR-485-3p/FGF2 axis

2020 ◽  
pp. jim-2020-001537
Author(s):  
Shanshan Wu ◽  
Shimei Liu ◽  
Huaihua Song ◽  
Jiayu Xia
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Circular Rna ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Pcr Assay ◽  
Fgf2 Expression ◽  
Proliferation And Metastasis ◽  
Dual Luciferase Reporter Assay

Circular RNA (circRNA) is an endogenous RNA molecule with a stable closed-loop structure. The circular RNA HIPK3 (circHIPK3) is highly expressed in hepatocellular carcinoma and facilitates tumor growth. However, its role in cervical cancer (CC) and its regulatory mechanisms are not well-studied. This study aimed for investigating the function of circHIPK3 on proliferation and metastasis of CC cells. In this study, quantitative real-time PCR assay was adopted to delve into the circHIPK3 expression in CC cell lines. Cell counting kit-8 and colony formation assays were used to evaluate the influence of overexpression and knockdown of circHIPK3 on CC cell proliferation. Dual-luciferase reporter assay was employed to probe into the binding of miR-485-3p to circHIPK3 and miR-485-3p to the 3’ untranslated region (UTR) of fibroblast growth factor 2 (FGF2), respectively. FGF2 protein expression was detected by western blot analysis. This study confirmed that circHIPK3 was highly expressed in CC tissues. Overexpressed circHIPK3 could remarkably expedite the proliferation, migration and invasion of SiHa cells, and knocking down circHIPK3 could significantly impede the proliferation, migration and invasion of HeLa cells. MiR-485-3p can directly bind to circHIPK3 and the 3’UTR of FGF2. Overexpression of circHIPK3 triggered the upregulation of FGF2 expression while knockdown of circHIPK3 reduced FGF2 expression in CC cells, and the transfection of miR-485-3p mimics reversed the upregulation of FGF2 expression and enhanced malignant phenotypes in CC cells with overexpressed circHIPK3.

scholarly journals The novel circ_0028171/miR-218-5p/IKBKB axis promotes osteosarcoma cancer progression

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Feng Pan ◽  
Jun Zhang ◽  
Benseng Tang ◽  
Li Jing ◽  
Bing Qiu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Bone Cells ◽  
Human Cancer ◽  
Underlying Mechanism ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion

Abstract Background Recently, it has been demonstrated that circular RNA (circRNA) contributes to the production and progression in human cancer. However, the specific function and underlying mechanism of circ_0028171 in osteosarcoma (OS) still remain largely unclear and require to be investigated. Methods In our study, we confirmed differentially expressed circRNAs by microarray analysis in normal bone cells vs. OS cell lines. The expression of circ-0028171 in OS was measured by qRT-PCR. Nuclear-cytoplasmic fractionation was employed to identify the localization of circ-0028171, and RNase R and actinomycin D treatment were used to prove its circular characteristic. In vitro experiments, such as CCK-8 method, cell count, cell colony formation, transwell migration and invasion assays, and in vivo tumor models were adopted to evaluate the effect of circ_0028171. Further, luciferase reporter, RIP and RNA pull-down assays were conducted to confirm the binding sites of circ_0028171 with miR-218-5p. Results We found that circ_0028171 displayed a remarkably higher expression in both OS tissues and cell lines. Circ_0028171 mainly located in the cytoplasm as a stable cyclic transcript. Knockdown of circ_0028171 suppressed OS tumor growth in vitro and in vivo, while up-regulated circ_0028171 remarkably enhanced cell proliferation, migration and invasion abilities in OS. Several mechanistic experiments revealed that circ_0028171 served as a sponge of miR-218-5p to increase IKBKB expression. Conclusions our research reveals that circ_0028171 might promote the malignant behavior of OS tissues through miR-218-5p/IKBKB axis, which could be a potential novel marker for early diagnosis of OS.

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