scholarly journals KIF3A Inhibits NPC Proliferation, Migration and Invasion By Interacting With β-Catenin To Suppress Its Nuclear Accumulation

2021 ◽  
Author(s):  
Zhe Hu ◽  
Jinlan Meng ◽  
Hongbing Cai ◽  
Na Ma ◽  
Xiujie Gao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Southern China ◽  
Underlying Mechanism ◽  
Nuclear Accumulation ◽  
Migration And Invasion ◽  
Promising Therapeutic Target ◽  
Epithelial Tumour ◽  
Incorporation Assay

Abstract Background Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumour that is prevalent in Southern China and other Southeast Asian countries. In previous studies, Kinesin Family Member 3A (KIF3A) was shown to play a dual role in cancers. However, the biological role of KIF3A in NPC and the underlying mechanism have not been reported. Methods The KIF3A mRNA and protein expressions in NPC were analyzed by qRT-PCR (Quantitative real-time polymerase chain reaction), Western blotting and immunohistochemistry. CCK-8, EDU incorporation assay, Colony formation, cell cycle assay, Wound-Healing Assay, Transwell verified KIF3A regulates the proliferation, migration, invasion of NPC cells. The in vivo effect of KIF3A on proliferation was elucidated with a xenograft mouse model. COIP (Co-immunoprecipitation) assay showed KIF3A interacts with β-catenin. Confocal microscopy colocalization assay confirmed colocalization of KIF3A and β-catenin in NPC cells. Nuclear and cytoplasmic extraction assays were performed to analyze the distribution of β-catenin in the nuclei and cytoplasm. Results In this study, we found that KIF3A interacts with β-catenin, suppressing the intranuclear aggregation of β-catenin, then inactivating the Wnt/β-catenin signaling pathway as well as the downstream cell cycle factors and EMT signal to inhibit NPC proliferation, migration, and invasion. Conclusions These findings suggest that KIF3A interacts with β-catenin and attenuates the malignant progression of NPC by inhibiting β-catenin intranuclear aggregation. KIF3A may be a promising therapeutic target for NPC patients.

scholarly journals miR-188-5p Suppresses Gastric Cancer Cell Proliferation and Invasion via Targeting ZFP91

2018 ◽  
Vol 27 (1) ◽  
pp. 65-71 ◽  
Author(s):  
Yuping Peng ◽  
Xuning Shen ◽  
Honggang Jiang ◽  
Zhiheng Chen ◽  
Jiaming Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Inverse Correlation ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Promising Therapeutic Target ◽  
Cellular Apoptosis ◽  
Gastric Cancer Cell Proliferation

MicroRNAs (miRNAs) have been demonstrated to be essential regulators in the development and progression of various cancers. The role of miR-188-5p in gastric cancer (GC) has not been determined. In this study, we found that the expression of miR-188-5p was downregulated in GC tissues compared with adjacent normal tissues. The lowly expressed miR-188-5p was significantly associated with lymph node metastasis and advanced TNM stage. Moreover, overexpression of miR-188-5p significantly inhibited GC cell proliferation, migration, and invasion but promoted cellular apoptosis. Mechanistically, we identified transcription factor ZFP91 as a target gene of miR-188-5p in GC. We found that miR-188-5p overexpression significantly inhibited the expression of ZFP91 in GC cell lines. There was an inverse correlation between the expression of miR-188-5p and ZFP91 in GC tissues. We found that restoration of ZFP91 in miR-188-5p-overexpressed MGC-803 and SGC-7901 cells promoted cell proliferation, migration, and invasion. Finally, we also showed that overexpression of miR-188-5p inhibited tumor growth in vivo. Taken together, our findings indicated that miR-188-5p serves as a tumor suppressor in human GC by targeting ZFP91, suggesting that miR-188-5p might be a promising therapeutic target for GC treatment.

scholarly journals CircNFIX promotes progression of glioma through regulating miR-378e/RPN2 axis

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Chenyu Ding ◽  
Zanyi Wu ◽  
Honghai You ◽  
Hongliang Ge ◽  
Shufa Zheng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Xenograft Model ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cell Cycle Distribution ◽  
Glioma Progression

Abstract Background Circular RNA nuclear factor I X (circNFIX) has been reported to play an important role in glioma progression. However, the mechanism by which circNFIX participates in glioma progression remains poorly understood. Methods GERIA online were used to analyze the abnormally expressed genes in glioma tissues. The expression levels of circNFIX, microRNA (miR)-378e and Ribophorin-II (RPN2) were measured by quantitative real-time polymerase chain reaction or western blot. Cell cycle distribution, apoptosis, glycolysis, migration and invasion were determined by flow cytometry, special kit and trans-well assays, respectively. The target association between miR-378e and circNFIX or RPN2 was confirmed by luciferase reporter assay, RNA immunoprecipitation and pull-down. Xenograft model was established to investigate the role of circNFIX in vivo. Results The expression of circNFIX was enhanced in glioma tissues and cells compared with matched controls and high expression of circNFIX indicated poor outcomes of patients. Knockdown of circNFIX led to arrest of cell cycle, inhibition of glycolysis, migration and invasion and promotion of apoptosis in glioma cells. circNFIX was a sponge of miR-378e. miR-378e overexpression suppressed cell cycle process, glycolysis, migration and invasion but promoted apoptosis. miR-378e silence abated the suppressive role of circNFIX knockdown in glioma progression. RPN2 as a target of miR-378e was positively regulated via circNFIX by competitively sponging miR-378e. Silencing circNFIX decreased glioma xenograft tumor growth by regulating miR-378e/RPN2 axis. Conclusion Knockdown of circNFIX inhibits progression of glioma in vitro and in vivo by increasing miR-378e and decreasing RPN2, providing a novel mechanism for understanding the pathogenesis of glioma.

scholarly journals UBE2T-regulated H2AX monoubiquitination induces hepatocellular carcinoma radioresistance by facilitating CHK1 activation

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Jingyuan Sun ◽  
Zhenru Zhu ◽  
Wenwen Li ◽  
Mengying Shen ◽  
Chuanhui Cao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Dna Repair ◽  
Clinical Data ◽  
Underlying Mechanism ◽  
Cell Cycle Checkpoint ◽  
Cell Cycle Checkpoints

Abstract Background Radioresistance is the major obstacle in radiation therapy (RT) for hepatocellular carcinoma (HCC). Dysregulation of DNA damage response (DDR), which includes DNA repair and cell cycle checkpoints activation, leads to radioresistance and limits radiotherapy efficacy in HCC patients. However, the underlying mechanism have not been clearly understood. Methods We obtained 7 pairs of HCC tissues and corresponding non-tumor tissues, and UBE2T was identified as one of the most upregulated genes. The radioresistant role of UBE2T was examined by colony formation assays in vitro and xenograft tumor models in vivo. Comet assay, cell cycle flow cytometry and γH2AX foci measurement were used to investigate the mechanism by which UBE2T mediating DDR. Chromatin fractionation and immunofluorescence staining were used to assess cell cycle checkpoint kinase 1(CHK1) activation. Finally, we analyzed clinical data from HCC patients to verify the function of UBE2T. Results Here, we found that ubiquitin-conjugating enzyme E2T (UBE2T) was upregulated in HCC tissues, and the HCC patients with higher UBE2T levels exhibited poorer outcomes. Functional studies indicated that UBE2T increased HCC radioresistance in vitro and in vivo. Mechanistically, UBE2T-RNF8, was identified as the E2-E3 pair, physically bonded with and monoubiquitinated histone variant H2AX/γH2AX upon radiation exposure. UBE2T-regulated H2AX/γH2AX monoubiquitination facilitated phosphorylation of CHK1 for activation and CHK1 release from the chromatin to cytosol for degradation. The interruption of UBE2T-mediated monoubiquitination on H2AX/γH2AX, including E2-enzyme-deficient mutation (C86A) of UBE2T and monoubiquitination-site-deficient mutation (K119/120R) of H2AX, cannot effectively activate CHK1. Moreover, genetical and pharmacological inhibition of CHK1 impaired the radioresistant role of UBE2T in HCC. Furthermore, clinical data suggested that the HCC patients with higher UBE2T levels exhibited worse response to radiotherapy. Conclusion Our results revealed a novel role of UBE2T-mediated H2AX/γH2AX monoubiquitination on facilitating cell cycle arrest activation to provide sufficient time for radiation-induced DNA repair, thus conferring HCC radioresistance. This study indicated that disrupting UBE2T-H2AX-CHK1 pathway maybe a promising potential strategy to overcome HCC radioresistance.

scholarly journals Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

2018 ◽  
Vol 51 (3) ◽  
pp. 1364-1375 ◽  
Author(s):  
Dan Fei ◽  
Xiaona Zhang ◽  
Jinxiang Liu ◽  
Long Tan ◽  
Jie Xing ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Colony Formation ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Qrt Pcr

Background/Aims: Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to play crucial regulatory roles in tumor progression. However, its clinical significance and biological role in osteosarcoma (OS) is completely unknown. The aim of the present study was to investigate the role of FER1L4 in OS progression and the underlying mechanism. Methods: We analyzed the expression levels of FER1L4 in tissues of OS patients and cell lines via quantitative RT-PCR (qRT-PCR). The effect of FER1L4 on cell proliferation, colony formation, migration and invasion was analyzed by cell counting kit-8 (CCK-8), colony formation, wound healing and transwell invasion assay, respectively. Novel targets of FER1L4 were selected through a bioinformatics soft and confirmed using a dual-luciferase reporter system and qRT-PCR. To detect the role of FER1L4 in vivo tumorigenesis, tumor xenografts were created. Results: We found that the expression of FER1L4 was significantly downregulated in OS tissues and cell lines; moreover, low expression of FER1L4 was associated with advanced tumor-nude-metastasis (TNM) stage, lymph node metastases, and poor overall survival. Functional assays showed that upregulation of FER1L4 significantly inhibited OS cell proliferation, colony formation, migration, and invasion in vitro, as well as suppressed tumor growth in vivo. Assays performed to determine the underlying mechanism, indicated that FER1L4 interacted directly with miR-18a-5p. Subsequently, we found that FER1L4 significantly increased PTEN expression, a known target of miR-18a-5p, in OS cells. Furthermore, PTEN was found to be down-regulated, and positively correlated with FER1L4 in OS tissues. Conclusion: These findings suggest that FER1L4, acting as a competing endogenous RNA (ceRNA) of miR-18a-5p, exerts its anti-cancer role by modulating the expression of PTEN. Thus, FER1L4 may be a novel target for the prevention and treatment of OS.

scholarly journals FEZF1-AS1 is a key regulator of cell cycle, epithelial–mesenchymal transition and Wnt/β-catenin signaling in nasopharyngeal carcinoma cells

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Yunzhou Cheng
Keyword(s):  
Cell Cycle ◽  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Expression Levels

AbstractBackground: Accumulating studies discloses that long non-coding RNAs (lncRNAs) serve important roles in human tumorigenesis, including nasopharyngeal carcinoma (NPC). The purpose of the present study was to determine the role of lncRNA FEZF1-AS1 in NPC.Materials and methods: The expression levels of FEZF1-AS1 in NPC tissues and cell lines were detected by RT-qPCR analysis. MTT assay was performed to investigate the proliferation of NPC cells in vitro, whereas the migration and invasion of NPC cells were determined by wound healing assay and transwell assay. A nude mouse tumor model was established to study the role of FEZF1-AS1 in NPC tumorigenesis in vivo. The expression levels of proteins were detected by Western blot assay.Results: The results showed that FEZF1-AS1 expression was increased in the NPC tissues and cell lines, and the higher expression of FEZF1-AS1 was closely associated with poor prognosis of NPC patients. We further observed that knockdown of FEZF1-AS1 inhibited the proliferation of NPC cells in vitro and suppressed NPC xenograft growth in vivo through inducing G2/M cell cycle arrest. The migratory and invasive abilities of NPC cells were also reduced upon FEZF1-AS1 knockdown. Moreover, we demonstrated that inhibition of FEZF1-AS1 remarkably suppressed epithelial–mesenchymal transition (EMT) and reduced β-catenin accumulation in nucleus in NPC cells.Conclusions: Collectively, we showed that FEZF1-AS1 might be a key regulator of cell cycle, EMT and Wnt/β-catenin signaling in NPC cells, which may be helpful for understanding of pathogenesis of NPC.

scholarly journals miR-126a-3p induces proliferation, migration and invasion of trophoblast cells in pre-eclampsia-like rats by inhibiting A Disintegrin and Metalloprotease 9

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Shenglong Zhao ◽  
Jiandong Wang ◽  
Zheng Cao ◽  
Lei Gao ◽  
Yuanyuan Zheng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Wound Healing ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Cell Cycle Distribution ◽  
Wound Healing Assay ◽  
Trophoblast Cells ◽  
Transwell Assay ◽  
Blank Group

Abstract The present study aimed to investigate the underlying mechanism of miR-126a-3p in the proliferation, migration and invasion of trophoblast cells in pre-eclampsia-like rats by targeting A Disintegrin and Metalloprotease 9 (ADAM9). First, the interaction between miR-126a-3p and ADAM9 was confirmed via biochemical assays. Placental tissues and trophoblast cells were then obtained. RNA in situ hybridization was performed in order to detect miR-126a-3p expression in the placenta. Subsequently, a series of biological assays, including reverse transcription-quantitative PCR (RT-qPCR), Western blotting, MTT assay, apoptosis assay, cell cycle assay, wound healing assay and transwell assay were adopted in order to determine the cell proliferation, cell cycle distribution, apoptotic rate, and migration and invasion of trophoblast cells in each group. The results revealed that miR-126a-3p was down-regulated in the placenta of pre-eclampsia-like rats. In vivo experiments’ results indicated that miR-126a-3p could inhibit ADAM9 expression, and induce cyclin D1, Matrix metalloproteinase (MMP) 2 (MMP-2), MMP-9 expression. MTT, apoptosis and cell cycle assay results revealed that trophoblast cells transfected with miR-126a-3p mimic or si-ADAM9 exhibited higher proliferative activity and a lower apoptotic rate compared with the blank group (all P<0.05). The wound healing assay and transwell assay results confirmed that, compared with the blank group, the migration and invasion ability of trophoblast cells in the miR-126a-3p mimic group and small interfering RNA (siRNA)-ADAM9 group were significantly increased (all P<0.05). Conversely, miR-126a-3p inhibitor treatment revealed the opposite effect (all P<0.05). In conclusion, the present study demonstrated that miR-126a-3p could enhance proliferation, migration and invasion, but decrease the apoptosis rate of trophoblast cells in pre-eclampsia-like rats through targeting ADAM9.

scholarly journals Long noncoding RNA CYTOR sponges miR-195 to modulate proliferation, migration, invasion and radiosensitivity in nonsmall cell lung cancer cells

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Jun Zhang ◽  
Wenqi Li
Keyword(s):  
Lung Cancer ◽  
Cell Lung Cancer ◽  
Noncoding Rna ◽  
Nonsmall Cell Lung Cancer ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Functional Roles ◽  
Promising Therapeutic Target ◽  
Microrna Sponge

Nonsmall cell lung cancer (NSCLC) is one of the most frequent malignancies worldwide. Long noncoding RNAs (LncRNAs) play critical roles in cancer initiation and progression. Previous studies have demonstrated that overexpression of cytoskeleton regulator RNA (CYTOR) predicates poor prognosis and promotes tumor progression. However, the functional roles and underlying mechanism of CYTOR in NSCLC remain unknown. In the present study, we found that CYTOR promoted cell proliferation, migration and invasion ability, and induced radioresistance in NSCLC cells. Mechanistically, CYTOR could directly interact with miR-195 and increase its targets. Thus, CYTOR played an oncogenic role in NSCLC progression through sponging miR-195. Together, our study elucidates the role of CYTOR as a microRNA sponge in NSCLC, and CYTOR may be used as a promising therapeutic target for NSCLC treatment.

Use of co-expression of HGF and c-Met to predict peritoneal dissemination established by autocrine HGF/c-Met signaling in gastric cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 40-40 ◽  
Author(s):  
Y. Toiyama ◽  
K. Tanaka ◽  
H. Yasuda ◽  
S. Saigusa ◽  
H. Fujikawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Peritoneal Dissemination ◽  
Biological Effects ◽  
Immunohistochemical Analysis ◽  
Migration And Invasion ◽  
Migration Ability ◽  
Epithelial Tumour

40 Background: Epithelial mesencymal transition (EMT) promotes facilitates migration and invasion of epithelial tumour cells. EMT is induced by growth factors implicated in theses process such as hepatocyte growth factor (HGF). Our aim of this study is whether HGF/c-Met pathway is associated with metastasis of gastric cancer (GC), especially in peritoneal dissemination (PD). Methods: HGF and c-Met expression and EMT related molecules were evaluated using real-time PCR and immunohistochemistry in GC tissues. The role of HGF/c-Met pathway for EMT and anoikis was determined and c-Met TKI (SU11274) was tested for their ability to block HGF-induced biological effects in vitro and vivo. Results: In HGF(-)c-Met(+) GC cells,recombinant HGF promoted EMT phenotype characterized by morphology, impaired E-cadherin and induction of Vimentin. HGF promoted cell growth, invasiveness, migration ability and inhibition of anoikis. SU11274 blocked HGF-induced EMT and the biological effects in vitro. In contrast of HGF(+)c-Met(+) GC cells, HGF exposure was not affected biological outcome of EMT and anoikis but SU11274 blocked biological effect as same as in HGF(-)c-Met(+) GC cells. In vivo, HGF(+)c-Met(+) GC cell line only established PD and SU11274 intraperitoneally caused an inhibition of PD growth. Clinically, HGF expression was significantly positive correlated with c-Met expression in GC specimens. Increased HGF and c-Met demonstrated a significantly associated with poor prognosis and can predict PD, respectively. Furthermore, HGF was one of the independent factors for predicting PD. Immunohistochemical analysis showed HGF and c-Met were predominantly co-expressed in cancer cell of both primary GC and PD. Conclusions: We have demonstrated that HGF/c-Met pathway as an inducer of EMT and anoikis inhibition in GC cell. Co-expression of HGF and c-Met implicates its potential to promote PD in GC. Blocking the autocrine HGF/c-Met pathway may be clinically useful for the treatment of PD in GC. No significant financial relationships to disclose.

scholarly journals Potential Role of SWI/SNF Complex Subunit Actin-Like Protein 6A in Cervical Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Qingying Wang ◽  
Zuozeng Cao ◽  
Yingze Wei ◽  
Jiawen Zhang ◽  
Zhongping Cheng
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cancer Cells ◽  
Colony Formation ◽  
Gene Set Enrichment Analysis ◽  
Migration And Invasion ◽  
Cancer Type

SWI/SNF complex subunit Actin-like protein 6A (ACTL6A) has been regarded as an oncogene, regulating the proliferation, migration and invasion of cancer cells. However, the expression pattern and biological role of ACTL6A in cervical cancer have not been reported. In this study, the mRNA expression and protein level of ACTL6A in cervical cancer samples were determined by public database and immunohistochemical (IHC) analysis. The effects of ACTL6A on cervical cancer cells were investigated via MTT, colony-formation assay, tumor xenografts and flow cytometry. Gene set enrichment analysis (GSEA) was used to explore the potential mechanism of ACTL6A in regulating tumorigenesis of cervical cancer. The results revealed that ACTL6A was markedly upregulated in cervical cancer tissues. Silencing ACTL6A expression resulted in decreased cervical cancer cell proliferation, colony formation and tumorigenesis in vitro and in vivo. Furthermore, we demonstrated that knockdown of ACTL6A induced cell cycle arrest at G1 phase, ACTL6A-mediated proliferation and cell cycle progression were c-Myc dependent. Our study provides the role of ACTL6A in cervical oncogenesis and reveals a potential target for therapeutic intervention in this cancer type.

scholarly journals LncRNA PVT1 promotes cervical cancer progression by sponging miR-503 to upregulate ARL2 expression

2021 ◽  
Vol 16 (1) ◽  
pp. 1-13
Author(s):  
Weiwei Liu ◽  
Dongmei Yao ◽  
Bo Huang
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Nude Mouse Model ◽  
Western Blot Assay ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Cervical cancer (CC) is a huge threat to the health of women worldwide. Long non-coding RNA plasmacytoma variant translocation 1 gene (PVT1) was proved to be associated with the development of diverse human cancers, including CC. Nevertheless, the exact mechanism of PVT1 in CC progression remains unclear. Levels of PVT1, microRNA-503 (miR-503), and ADP ribosylation factor-like protein 2 (ARL2) were measured by quantitative reverse transcription-polymerase chain reaction or western blot assay. 3-(4,5)-Dimethylthiazole-2-y1)-2,5-biphenyl tetrazolium bromide (MTT) and flow cytometry were used to examine cell viability and apoptosis, respectively. For migration and invasion detection, transwell assay was performed. The interaction between miR-503 and PVT1 or ARL2 was shown by dual luciferase reporter assay. A nude mouse model was constructed to clarify the role of PVT1 in vivo. PVT1 and ARL2 expressions were increased, whereas miR-503 expression was decreased in CC tissues and cells. PVT1 was a sponge of miR-503, and miR-503 targeted ARL2. PVT1 knockdown suppressed proliferation, migration, and invasion of CC cells, which could be largely reverted by miR-503 inhibitor. In addition, upregulated ARL2 could attenuate si-PVT1-mediated anti-proliferation and anti-metastasis effects on CC cells. Silenced PVT1 also inhibited CC tumor growth in vivo. PVT1 knockdown exerted tumor suppressor role in CC progression via the miR-503/ARL2 axis, at least in part.

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