scholarly journals MicroRNA-4325 Suppresses Cell Progression in Hepatocellular Carcinoma via GATA-Binding Protein 6

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xiaoxia Huo ◽  
Houmin Zhou ◽  
Tiantian Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Binding Protein ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Regulatory Function ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Tissue Specimens

MicroRNAs (miRs) are regulators of the formation and development of hepatocellular carcinoma (HCC). The biological role of miR-4325 in HCC has yet to be determined. This study is aimed at dissecting the role of miR-4325 in HCC and the underlying mechanism. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-4325 expression in HCC tissue specimens and cells. Cell proliferation, migration, and invasion were assessed by using the MTT assay and Transwell assay, respectively. The miR-4325 target was predicted based on bioinformatics analysis and validated using the dual-luciferase reporter assay. Rescue experiments in the cells were utilized to functionally characterize the downstream molecular targets of miR-4325. We observed that miR-4325 expression levels were significantly reduced in both HCC tissue specimens and cell lines. Meanwhile, a lower miR-4325 level was associated with a poorer prognosis. Gain and loss of function assays revealed that miR-4325 markedly downregulated HCC cell growth, migration, and invasion. Moreover, we identified GATA-binding protein 6 (GATA6) as a miR-4325 target and found that GATA6 was abnormally expressed in HCC. Rescue assays demonstrated that the regulatory function of miR-4325 in HCC was mediated by GATA6. Taken together, miR-4325 suppresses HCC cell growth, migration, and invasion by targeting GATA6, suggesting that miR-4325 may potentially serve as a novel therapeutic target for HCC.

scholarly journals Circular RNA hsa_circ_101555 promotes hepatocellular carcinoma cell proliferation and migration by sponging miR-145-5p and regulating CDCA3 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Xiaoguang Gu ◽  
Jianan Zhang ◽  
Yajuan Ran ◽  
Hena Pan ◽  
JinHong Jia ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Biological Effects ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Casein Kinase 1 ◽  
Mouse Xenograft Model ◽  
Hcc Cells

AbstractCircular RNAs have been reported to play significant roles in regulating pathophysiological processes while also guiding clinical diagnosis and treatment of hepatocellular carcinoma (HCC). However, only a few circRNAs have been identified thus far. Herein, we investigated the role of a specific closed-loop structure of hsa_circ_101555 that was generated by back-splicing of the host gene casein kinase 1 gamma 1 (CSNK1G1) in the development and proliferation of HCC. We investigated the expression of Hsa_circ_101555 in HCC and normal tissues using bioinformatics. The expression level of hsa_circ_101555 was further detected by fluorescence in situ hybridization and qRT-PCR in ten HCC patients. Transwell, migration, WST-1 assays, and colony formation assays were used to evaluate the role of hsa_circ_101555 in HCC development and proliferation. The regulatory mechanisms of hsa_circ_101555 in miR-145-5p and CDCA3 were determined by dual luciferase reporter assay. A mouse xenograft model was also used to determine the effect of hsa_circ_101555 on HCC growth in vivo. hsa_circ_101555 showed greater stability than the linear RNA; while in vitro and in vivo results demonstrated that hsa_circ_101555 silencing significantly suppressed cell proliferation, migration, and invasion of HCC cells. Rescue experiments further demonstrated that suppression of miR-145-5p significantly attenuated the biological effects of hsa_circ_101555 knockdown in HCC cells. We also identified a putative oncogene CDCA3 as a potential miR-145-5p target. Thus, our results demonstrated that hsa_circ_101555 might function as a competing endogenous RNA of miR-145-5p to upregulate CDCA3 expression in HCC. These findings suggest that hsa_circ_101555 may be a potential therapeutic target for patients with HCC.

Silencing of hsa_circ_0000515 Inhibits Proliferation, Migration and Invasion of Gastric Cancer Cells by Sponging miR-615-5p In Vitro

2021 ◽  
Vol 11 (8) ◽  
pp. 1466-1476
Author(s):  
Xuli Wang ◽  
Aiping Wang
Keyword(s):  
Gastric Cancer ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Circular Rnas ◽  
Loss Of Function ◽  
Gastric Cancer Cells ◽  
Novel Target

Circular RNAs (circRNAs) have been reported to participate in the molecular mechanism of human cancers. This study investigates the role of circRNA hsa_circ_0000515 in gastric cancer (GC) cells and the underlying mechanism associated with microRNA-615-5p (miR-615-5p). qRT-PCR analysis showed the upregulation of hsa_circ_0000515 and downregulation of miR-615-5p in GC cell lines. Loss-of-function experiments indicated that suppression of hsa_circ_0000515 inhibited cell proliferation, migration, and invasion. Dual-luciferase reporter assay highlighted that hsa_circ_0000515 was able to act as a ceRNA of miR-615-5p. Furthermore, hsa_circ_0000515 could interact with splicing factors and bind miR-615-5p to regulate progression of GC cells. Deficiency of miR-615-5p reverses the inhibitory roles of si-hsa_circ_0000515 on the proliferation, migration, and invasion of GC cells. The findings highlighted the promising uses of hsa_circ_0000515 as a likely novel target for gastric cancer treatment.

scholarly journals LINC00839 Knockdown Restrains The Metastatic Behaviors of Nasopharyngeal Carcinoma By Sponging miR-454-3p

2021 ◽  
Author(s):  
Feng Ying Zhang ◽  
Xia Li ◽  
Ting Ting Huang ◽  
Mei Ling Xiang ◽  
Lin Lin Sun ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Regulatory Function ◽  
Migration And Invasion ◽  
Luciferase Reporter Gene ◽  
Non Coding Rna ◽  
Invasive Capacity

Abstract Background Long intergenic non-coding RNA 00839 (LINC00839) has been verified as a cancer-promoting gene in malignancies. However, the significance of LINC00839 in nasopharyngeal carcinoma (NPC) has yet to be elaborated, as well as its underlying mechanism.Methods LINC00839 and miR-454-3p relative expression levels in NPC cells were examined by qRT-PCR. The growth of cells was examined by CCK-8 and colony formation assays. Cell migration and invasion were examined by wound healing and Transwell experiment, respectively. The binding sequence of LINC00839 and miR-454-3p was confirmed by the luciferase reporter gene experiment. The regulatory function of LINC00839 and miR-454-3p on c-Met was investigated by western blot.Results Here, we revealed that LINC00839 was elevated in NPC. Both LINC00839 knockdown and upregulation of miR-454-3p suppressed NPC cells proliferation, invasive capacity and EMT in vitro. Besides, LINC00839 was validated as a miR-454-3p “sponge”, and upregulation of LINC00839 could reverse miR-454-3p-mediated functions in NPC C666-1 and SUNE-1 cells. Furthermore, c-Met was determined to be targeted by miR-454-3p. Notably, c-Met was downregulated by LINC00839 knockdown through sponging miR-454-3p. In vivo, LINC00839 knockdown resulted in a slower tumor growth.Conclusions Altogether, knockdown of LINC00839 inhibits the aggressive properties of NPC cells via sponging miR-454-3p and regulating c-Met.

scholarly journals Circ_0000215 Exerts Oncogenic Function in Nasopharyngeal Carcinoma by Targeting miR-512-5p

2021 ◽  
Vol 9 ◽  
Author(s):  
Xinping Chen ◽  
Weihua Xu ◽  
Zhichao Ma ◽  
Juan Zhu ◽  
Junjie Hu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Cell Counting ◽  
Regulatory Subunit ◽  
Luciferase Reporter ◽  
Regulatory Function ◽  
Migration And Invasion ◽  
Circular Rnas

Background: Increasing circular RNAs (circRNAs) are reported to participate in cancer progression. Nonetheless, the role of circRNAs in nasopharyngeal carcinoma (NPC) has not been fully clarified. This work is aimed to probe the role of circ_0000215 in NPC.Methods: Circ_0000215 expression in NPC tissues and cell lines was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) assay, 5-bromo-2′-deoxyuridine (BrdU) assay, scratch healing assay and Transwell experiment were executed to investigate the regulatory function of circ_0000215 on the proliferation, migration and invasion of NPC cells. RNA immunoprecipitation (RIP), pull-down and dual-luciferase reporter experiments were utilized to determine the binding relationship between circ_0000215 and miR-512-5p, and between miR-512-5p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) 3′UTR. The effects of circ_0000215 on NPC growth and metastasis in vivo were examined with nude mice model. Western blot was applied to detect the regulatory effects of circ_0000215 and miR-512-5p on PIK3R1 expression.Results: Circ_0000215 was overexpressed in NPC tissues and cell lines. The functional experiments confirmed that knockdown of circ_0000215 impeded the growth and metastasis of NPC cells in vitro and in vivo. Additionally, circ_0000215 could also work as a molecular sponge to repress miR-512-5p expression. PIK3R1 was validated as a target gene of miR-512-5p, and circ_0000215 could increase the expression level of PIK3R1 in NPC cells via suppressing miR-512-5p.Conclusion: Circ_0000215 is overexpressed in NPC and exerts oncogenic effects in NPC through regulating miR-512-5p/PIK3R1 axis.

scholarly journals The Circ_0001367/miR-545-3p/LUZP1 Axis Regulates Cell Proliferation, Migration and Invasion in Glioma Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Xuchen Dong ◽  
Peng Zhang ◽  
Liang Liu ◽  
Haoran Li ◽  
Shan Cheng ◽  
...  
Keyword(s):  
Leucine Zipper ◽  
Cell Function ◽  
Glioma Cells ◽  
Malignant Tumour ◽  
Underlying Mechanism ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Loss Of Function

Glioma is the most common primary intracranial malignant tumour in adults. It has a high incidence and poses a serious threat to human health. Circular RNA is a hotspot of cancer research. In this study, we aimed to explore the role of circ_0001367 in gliomagenesis and the underlying mechanism. First, qRT-PCR was conducted, which showed that circ_0001367 level was downregulated in glioma tissues and cells. Next, gain-of-function and loss-of-function assays were performed, which indicated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells. Subsequent bioinformatics analysis, dual-luciferase reporter assays, RNA immunoprecipitation assays and cell function assays demonstrated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells by absorbing miR-545-3p and thereby regulating the expression of leucine zipper protein (LUZP1). Finally, an in vivo experiment was conducted, which demonstrated that circ_0001367 inhibited glioma growth in vivo by modulating miR-545-3p and LUZP1. Taken together, the results of this study demonstrate that the circ_0001367/miR-545-3p/LUZP1 axis may be a novel target for glioma therapy.

scholarly journals Long noncoding LINC00238 restrains Hepatocellular Carcinoma Malignant Phenotype via Sponging miR-522

2021 ◽  
Author(s):  
Honggang Qian ◽  
Qiong Wu ◽  
Jian-Hui Wu ◽  
Xiu-Yun Tian ◽  
Wei Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Cell Viability ◽  
Noncoding Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Malignant Phenotype ◽  
Migration Ability ◽  
Downstream Targets

Abstract Background: Long noncoding RNA (lncRNA) Can regulates tumor malignant phenotype either as a tumor suppressor or an oncogene. In hepatocellular carcinoma (HCC), the clinical significance and underlying mechanism of LINC00238 function remain undefined. Methods: Down-regulated expression levels of noncoding RNAs were screened from TCGA LIHC dataset through GEPIA software. The expression of RNAs were determined by qRT-PCR. Molecular clone was performed to over-expression and knockdown of LINC00238 expression. The levels of proteins were evaluated via Western blot. The cell viability, clone formation and migration ability were assessed by CCK-8, plate clone formation and Transwell assays. RNA pull down and Luciferase reporter assays were applied to detect the interplays between LINC00992 and miR-3935.Results: LINC00238 was identified as a significant downregulated both in TCGA and in our cohort, and its low expression was significantly correlated with bigger tumor size, early recurrence and poor survival of patients with HCC after surgery. Through the results of gain and loss of function experiments, LINC00238 was confirmed as a tumor suppressor， which could decrease not only cell viability, migration and invasion in vitro but also tumorigenesis and tumor metastasis in vivo. Mechanistically, RNA pull-down showed that LINC00238 sponged mir-522, and then, released the inhibition effects on two downstream targets, SFRP2 and DKK1.Conclusions: We identified LINC00238 as a tumor suppressor by sponging miR-522 followed by release silencing of downstream targets, suggesting that LINC00238 has a key role in restraining the malignant phenotype of HCC cells and providing a novel perspective on lncRNAs in HCC progression.

scholarly journals MicroRNA-183-5p contributes to malignant progression through targeting PDCD4 in human hepatocellular carcinoma

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Xiaohui Duan ◽  
Wei Li ◽  
Peng Hu ◽  
Bo Jiang ◽  
Jianhui Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Tumor Growth ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Hcc Cells

Abstract Hepatocellular carcinoma (HCC) remains one of the most common malignant tumors worldwide. The present study aimed to investigate the biological role of microRNA-183-5p (miR-183-5p), a novel tumor-related microRNA (miRNA), in HCC and illuminate the possible molecular mechanisms. The expression patterns of miR-183-5p in clinical samples were characterized using qPCR analysis. Kaplan–Meier survival curve was applied to evaluate the correlation between miR-183-5p expression and overall survival of HCC patients. Effects of miR-183-5p knockdown on HCC cell proliferation, apoptosis, migration and invasion capabilities were determined via Cell Counting Kit-8 (CCK8) assays, flow cytometry, scratch wound healing assays and Transwell invasion assays, respectively. Mouse neoplasm transplantation models were established to assess the effects of miR-183-5p knockdown on tumor growth in vivo. Bioinformatics analysis, dual-luciferase reporter assays and rescue assays were performed for mechanistic researches. Results showed that miR-183-5p was highly expressed in tumorous tissues compared with adjacent normal tissues. Elevated miR-183-5p expression correlated with shorter overall survival of HCC patients. Moreover, miR-183-5p knockdown significantly suppressed proliferation, survival, migration and invasion of HCC cells compared with negative control treatment. Consistently, miR-183-5p knockdown restrained tumor growth in vivo. Furthermore, programmed cell death factor 4 (PDCD4) was identified as a direct target of miR-183-5p. Additionally, PDCD4 down-regulation was observed to abrogate the inhibitory effects of miR-183-5p knockdown on malignant phenotypes of HCC cells. Collectively, our data suggest that miR-183-5p may exert an oncogenic role in HCC through directly targeting PDCD4. The current study may offer some new insights into understanding the role of miR-183-5p in HCC.

scholarly journals ORC6, Negatively Regulated by miR-1-3p, Promotes Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Hu Chen ◽  
Lequn Bao ◽  
Jianhua Hu ◽  
Dongde Wu ◽  
Xianli Tong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Regulatory Function ◽  
Migration And Invasion ◽  
Cycle Progression ◽  
Hcc Cells

BackgroundIn recent years, microRNA-1-3p (miR-1-3p) has been linked to the progression of multiple cancers, whereas little is known about its role in hepatocellular carcinoma (HCC). Herein, we investigated the function of miR-1-3p in HCC, and its regulatory function on origin recognition complex subunit 6 (ORC6).MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was performed for detecting the expression levels of miR-1-3p and ORC6 mRNA in HCC samples and cell lines. ORC6 expression at the protein level was quantified by Western blot. After gain-of-function and loss-of-function models were established, cell counting kit-8 (CCK-8) assays, Transwell assays, flow cytometry, and 5-Ethynyl-2′-deoxyuridine (EdU) assay were performed for examining cell proliferation, migration, invasion, cell cycle, and apoptosis. The targeting relationship between miR-1-3p and ORC6 was confirmed with bioinformatic analysis and dual-luciferase reporter assays.ResultsThe expression of miR-1-3p was reduced in HCC samples and cell lines. Overexpression of miR-1-3p suppressed the proliferation, migration, and invasion, and induced cell-cycle arrest and apoptosis of HCC cells, whereas the opposite effects were induced by miR-1-3p inhibition. ORC6 is identified as a novel target of miR-1-3p, the expression of which is negatively correlated with miR-1-3p expression in HCC tissues. ORC6 overexpression facilitated the proliferation, migration, invasion, and cell cycle progression, and reduced apoptosis of HCC cells, whereas the opposite effects were induced by ORC6 knockdown. What is more, ORC6 overexpression counteracted the biological functions of miR-1-3p in HCC cells.ConclusionMiR-1-3p targets ORC6 to suppress the proliferation, migration, invasion, and cell cycle progression, and promote apoptosis of HCC cells.

scholarly journals MicroRNA-139-3p Suppresses Tumor Growth and Metastasis in Hepatocellular Carcinoma by Repressing ANXA2R

2018 ◽  
Vol 26 (9) ◽  
pp. 1391-1399 ◽  
Author(s):  
Zeng Cheng Zou ◽  
Min Dai ◽  
Zeng Yin Huang ◽  
Yi Lu ◽  
He Ping Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Migration ◽  
Cell Growth ◽  
Mouse Model ◽  
Migration And Invasion ◽  
Tumor Growth And Metastasis ◽  
Underlying Mechanisms ◽  
Hcc Cells

The direct roles of miR-139-3p on hepatocellular carcinoma (HCC) cell growth and metastasis remain poorly understood. We attempted to demonstrate the regulatory role of miR-139-3p in HCC progression and its underlying mechanisms. Here we showed that miR-139-3p expression was significantly reduced in the HCC tissues compared to paratumor tissues. Exogenous overexpression of miR-139-3p inhibited the migration and invasion of HCC cells, whereas downregulation of miR-139-3p was able to induce HCC HepG2 and SNU-449 cell migration and invasion. In addition, miR-139-3p inhibited HCC growth and lung metastasis in an in vivo mouse model, which is mainly regulated by annexin A2 receptor (ANXA2R). Finally, we identified that the expression of miR-139-3p was inversely correlated with ANXA2R expression in human HCC tissue. All these results demonstrated that miR-139-3p inhibited the metastasis process in HCC by downregulating ANXA2R expression.

scholarly journals A novel lncRNA SOX2OT promotes the malignancy of human colorectal cancer by interacting with miR-194-5p/SOX5 axis

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Ye Feng ◽  
Ying Xu ◽  
Yongjian Gao ◽  
Yiying Chen ◽  
Xuefeng Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Functional Relationships ◽  
Rna Immunoprecipitation ◽  
Proliferation And Metastasis

AbstractLong noncoding RNAs (lncRNAs) show emerging roles in colorectal cancer (CRC) development and are considered to be involved in the potential mechanism of tumor malignancy. While Sox2 overlapping transcript (SOX2OT) has been implicated in the progression of multiple cancers, its role in CRC remains to be explored. In this study, in situ hybridization (ISH) and qRT-PCR were performed to establish the functional relationships between SOX2OT and CRC deranged in CRC tissue and cells. Subsequently, SOX2OT shRNAs vectors were transfected into CRC cells to performed loss-of-function assays to detect the potential role of SOX2OT on proliferation and metastasis in vitro and vivo. The results showed SOX2OT was an oncogene that was up-regulated in human CRC tissues and cell lines. SOX2OT silencing suppressed cell proliferation, migration, and invasion in CRC cells in vitro, and inhibited tumorigenesis in the mouse xenografts. Bioinformatic predictive analysis coupled with the dual-luciferase reporter, RNA immunoprecipitation (RIP), and functional rescue assay elucidated the mechanistic network of the SOX2OT-miR-194-5p-SOX5 axis in CRC. Mechanistically, SOX2OT acted as a competing endogenous RNA (ceRNA) to upregulate SOX5 by sponging miR-194-5p. Downregulated SOX2OT boosted miR-194-5p expression, thus decreased the protein level of SOX5, which suppresses tumorgenesis of CRC.

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