The profile analysis of circular RNAs in cervical cancer

Cervical cancer (CC) is the third most common cancer among women and has a high mortality rate at the advanced stage. The mechanisms underlying the development and progression of CC are still elusive. Circular RNAs (circRNAs) play an important role in various physiological and pathological processes. The aim of this study was to identify the circRNAs significantly associated with cervical squamous cell carcinoma (CSCC), in order to discover novel diagnostic markers and elucidate their mechanistic basis.The circRNA expression profiles of CSCC and paired para-cancerous cervical tissues was downloaded from the Gene Expression Omnibus. Bioinformatics analysis were used to screen for the differentially expressed circRNAs (DECRs). The expression levels of hsa_circ_0000745, hsa_circ_0084927, hsa_circ_0002762, hsa_circ_0075341, hsa_circ_0007905, hsa_circ_0031027, hsa_circ_0065898, hsa_circ_0070190, and hsa_circ_0078383 were verified in CC and normal cervical tissues by quantitative real-time PCR.A total of 197 DECRs were identified between the CSCC and normal tissues, including 87 upregulated and 110 downregulated circRNAs. In addition, 37 miRNAs were predicted for the upregulated circRNAs and 39 for the downregulated circRNAs. Functional analysis showed that the DECRs were associated with positive regulation of substrate adhesion-dependent cell spreading, metabolism, positive regulation of GTPase activity, protein regulation, and intercellular adhesion. The MAPK signaling pathway that plays a significant role in the progression of CC, was also enriched. Consistent with the in-silico analysis, hsa_circ_0000745, hsa_circ_0084927, hsa_circ_0002762, hsa_circ_0007905 were upregulated and hsa_circ_0078383 was downregulated in CC tissues (P < .001), whereas hsa_circ_0075341 (P < .001) and hsa_circ_0031027 (P = .001) showed opposite trends.We identified novel diagnostic and therapeutic biomarkers of CSCC along with the mechanistic basis.     

Clinicopathological and prognostic significance of circRNAs in lung cancer: A systematic review and meta-analysis

Background:Circular RNAs (circRNAs) regulate multiple pathways during lung cancer pathogenesis. Apart from functional significance, many circRNAs have been shown to be associated with clinicopathological characteristics and predict lung cancer prognosis. Our aim is to summarize the expanding knowledge of clinical roles of circRNAs in lung cancer.Methods:A thorough search of literature was conducted to identify articles about the correlation between circRNA expression and its prognostic and clinicopathological values. Biological mechanisms were summarized.Results:This study included 35 original articles and 32 circRNAs with prognostic roles for lung cancer. Increased expression of 25 circRNAs and decreased expression of 7 circRNAs predicted poor prognosis. For non-small cell lung cancer, changes of circRNAs were correlated with tumor size, lymph node metastasis, distant metastasis, tumor node metastasis (TNM) stage, and differentiation, indicating the major function of circRNAs is to promote lung cancer invasion and migration. Particularly, meta-analysis of ciRS-7, hsa_circ_0020123, hsa_circ_0067934 showed increase of the 3 circRNAs was associated with positive lymph node metastasis. Increase of ciRS-7 and hsa_circ_0067934 was also related with advanced TNM stage. The biological effects depend on the general function of circRNA as microRNA sponge.Conclusions:CircRNAs have the potential to function as prognostic markers and are associated with lung cancer progression and metastasis.     

Circ-PRMT5 enhances the proliferation,migration and glycolysis of hepatoma cells by targeting miR-188-5p/HK2 axis

Introduction and objectivesCircular RNA (circRNA) has been demonstrated as a critical regulator in human cancer, including hepatocellular carcinoma (HCC). Nevertheless, the role of circ-PRMT5 in HCC remains largely unknown.Patients or materials and methodsThe real-time quantitative polymerase chain reaction (RT-qPCR) was performed to assess the expression levels of circ-PRMT5, miR-188-5p and anti-Hexokinase II (HK2) in HCC tissues and cells. The cell proliferation, migration and glycolysis were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT), transwell migration assay, and indicated kits, respectively. The interaction relationship between miR-188-5p and circ-PRMT5 or HK2 was analyzed by the bioinformatics database, dual-luciferase reporter assay, and RNA immunoprecipitation (RIP) assay. The western blot assay was used to analyze the expression level of HK2. The functional role of circ-PRMT5 in vivo was assessed by a xenograft experiment.ResultsCirc-PRMT5 was elevated in HCC tissues and cells than matched control groups. Furthermore, loss-of-functional experiments revealed that the silencing of circ-PRMT5 could repress proliferation, migration, glycolysis in vitro and tumor growth in vivo. Moreover, we also confirmed that overexpression of circ-PRMT5 abolished the effects on HCC cells induced by upregulating miR-188-5p. In addition, overexpression of miR-188-5p could repress the development of HCC. More importantly, HK2 was a target gene of miR-188-5p, and miR-188-5p regulated proliferation, migration, glycolysis of HCC cells by specifically binding to HK2. Mechanistically, circ-PRMT5 could act as a sponge of miR-188-5p to regulate the expression of HK2.ConclusionIn summary, circ-PRMT5 might play a key role in proliferation, migration, glycolysis of HCC cells via miR-188-5p/HK2 axis, which indicated that circ-PRMT5 might be a potential therapeutic target for HCC treatment.     

Reduced expression of circRNA novel_circ_0005280 and its clinical value in the diagnosis of non-small cell lung cancer

BackgroundCircular RNAs (circRNAs) are a class of novel RNAs with important biologic functions. The aberrant expression of circRNAs has been implicated in human diseases; however, the clinical significance of circRNAs in non-small cell lung cancer (NSCLC) is still unclear. The aim of the present study was to evaluate the expression and clinical implications of novel_circ_0005280 in patients with NSCLC.MethodsWe evaluated differential circRNA expression in cancer and adjacent normal tissues from 3 patients with NSCLC via RNA sequencing. Among these circRNAs, 17 and 64 circRNAs showed higher and lower expressions, respectively. Novel_circ_0005280 expression in cancer tissues (n=41) was examined using quantitative real-time polymerase chain reaction, and the results are presented in the form of paired graph and scatter graph and its correlation with clinicopathological features and patient prognosis was analyzed by drawing receiver-operating characteristic (ROC) curve and Kaplan-Meier survival analysis.ResultsNovel_circ_0005280 expression was significantly decreased in NSCLC tumor tissues (n=41, obtained via biopsies), compared with adjacent normal tissues (n=27). Novel_circ_0005280 expression was correlated with tumor diameter and age. The area under the receiver-operating characteristic curve, cutoff, sensitivity, and specificity of novel_circ_0005280 were 0.944, 10.23, 85.2%, and 95.1%, respectively. Low novel_circ_0005280 expression was associated with a worse prognosis.ConclusionsNovel_circ_0005280 may be a useful biomarker for the diagnosis and prognosis of NSCLC.     

Integrated analysis of circRNAs and mRNAs expression profile revealed the involvement of hsa_circ_0007919 in the pathogenesis of ulcerative colitis

Background

Ulcerative colitis (UC) is characterized by chronic inflammation in the colon and epigenetic factors underlying the occurrence. Circular RNAs (circRNAs) have been under intensive focus due to the circular construct and gene-regulating functions. However, the changes and roles of circRNAs in UC remain unknown.

Methods

Microarrays were used to detect the differentially expressed genes, and quantitative real-time PCR was used to identify the changes in UC. In silico analyses were performed to predict the functions of circRNAs and mRNAs. In vitro, epithelial cell lines were stimulated by pro-inflammation effectors to test the alterations in circRNAs. CircRNAs–microRNAs–mRNAs network clarified the potential mechanisms underlying circRNAs in UC. The binding site between hsa_circ_0007919 and miR-138 or let-7a was verified using dual-luciferase assay.

Results

A total of 264 significantly dysregulated circRNAs and 1869 differentially expressed mRNAs in inflamed mucosa were compared with the non-inflamed mucosa in UC. Hsa_circ_0004662 and hsa_circ_0007919 were altered largely in UC tissues. Hsa_circ_0007919 was reduced persistently after inflammatory treatments, and it was relevant to Mayo endoscopic subscores and the expression of tight junction molecules. Finally, hsa_circ_0007919 could harbor miR-138, and let-7a to regulate the targeted mRNAs EPC1 and VIPR1.

Conclusions

Several circRNAs were differentially expressed in UC. Hsa_circ_0007919 is related to clinical characteristics and epithelial integrity by binding to hsa-let-7a, hsa-miR-138 to regulate the target genes. CircRNAs, especially hsa_circ_0007919, are associated with the pathogenesis and development of UC, with potential diagnostic and therapeutic implications.

     

Circ_0008285 knockdown represses tumor development by miR-384/RRM2 axis in hepatocellular carcinoma

Introduction and objectivesCircular RNA (circRNA) has attracted extensive attention in studies related to the malignant progression of cancer, including hepatocellular carcinoma (HCC). Therefore, its molecular mechanism in HCC needs to be further explored.Materials and methodsThe expression levels of circ_0008285, microRNA (miR)-384 and ribonucleotide reductase subunit M2 (RRM2) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was analyzed using cell counting kit-8 assay and 5-ethynyl-2’-deoxyuridine assay, cell apoptosis was analyzed by flow cytometry, and cell migration and invasion were detected by transwell assay. Protein level was detected by western blot. The relationships between miR-384 and circ_0008285 or RRM2 were predicted by bioinformatics software and validated by dual luciferase reporter assay and RNA immunoprecipitation (RIP) assay.ResultsCirc_0008285 expression is elevated to HCC tissues and cell lines. Silencing of circ_0008285 inhibited the proliferation, migration and invasion of HCC cells but accelerated cell apoptosis in vitro and impeded HCC tumorigenesis in vivo. Mechanistically, circ_0008285 directly interacted with miR-384, and miR-384 silencing attenuated the effects of circ_0008285 interference on cell proliferation, migration, invasion, and apoptosis. RRM2 was a direct target of miR-384, and RRM2 overexpression reversed the effects of miR-384 overexpression on cell proliferation, migration, invasion, and apoptosis. In addition, circ_0008285 regulated RRM2 expression by sponging miR-384.ConclusionIn this study, circ_0008285 could promote the malignant biological behaviors of HCC cells through miR-384/RRM2 axis and has the potential to become a therapeutic target for HCC, providing a new idea for targeted therapy of HCC.     

环状RNA hsacirc0001445在绝经后骨质疏松症患者中的表达及作用机制

目的探讨环状RNA(circRNA)hsa_circ₀001445在绝经后骨质疏松症(PMOP)患者中的临床意义和调控机制。方法从临床收集的血液样品中提取RNA, 使用实时荧光定量PCR(qRT-PCR)检测hsa_circ₀001445的表达。荧光素酶报告基因分析、RNA下拉实验研究了RNA之间的相互作用。结果与健康对照组相比, PMOP患者血浆hsa_circ₀001445表达下调(P<0.001)。血浆中hsa_circ₀001445以高灵敏度和特异性将PMOP患者与健康对照组区分开来, 曲线下面积(AUC)为0.9654(95%CI0.9361～0.9947, P<0.001), 灵敏度为94.0%, 特异度为88.0%。Hsa_circ₀001445促进人骨髓间充质干细胞(hBMSCs)的成骨分化、抑制成脂分化(P<0.001)。Hsa_c     

circZFR promotes cell proliferation and migration by regulating miR-511/AKT1 axis in hepatocellular carcinoma

BackgroundEmerging data suggest the crucial regulatory roles of circular RNAs (circRNAs) in hepatocellular carcinoma (HCC). However, the pathophysiology role of circZFR in HCC remains largely unknown.AimsThis study aims to disclose the functions of circZFR in HCC progression and its potential molecular mechanism.MethodscircZFR and miR-511 were identified by qRT-PCR. Colony formation assay, wound-healing assay, transwell assay, and flow cytometry assay were performed to determine the cell proliferation, migration, invasion and apoptosis. Western blotting and immunohistochemistry (IHC) were utilized to evaluate the expression level of AKT1, GSK3β, β-catenin and cascades of proliferation-related proteins both in vitro and in vivo. Dual luciferase reporter assay was conducted to evaluate the interactions among circZFR, miR-511 and AKT1.ResultsThe expression of circZFR was enhanced and the expression of miR-511 was down-regulated in HCC tissues and cells. Functionally, circZFR silencing or miR-511 overexpression suppressed cell proliferation, migration and invasion, and induced apoptosis of HCC cells. Mechanistically, circZFR acted as a miR-511 sponge to up-regulate its target gene AKT1, which activated cascades of proliferation-related proteins (c-Myc, cyclin D1, Survivin and Bcl-2). Furthermore, depletion of circZFR inhibited tumorigenesis and decreased the expression level of AKT1 in xenograft models.ConclusioncircZFR promotes HCC progression by directly down-regulating miR-511 to activate AKT1 signaling, suggesting that circZFR is a potential target in HCC treatment. Targeting circZFR may provide therapeutic benefits for HCC.     

Profiling and bioinformatics analyses reveal differential circular RNA expression in hypertensive patients

Objectives: CircRNAs, a novel class of noncoding RNAs, have been reported in many diseases. However, their role in hypertension remains unclear. Here, we aimed to determine the circRNA expression profile in hypertension patients and further construct a circRNA–miRNA–mRNA network for mechanism exploration. Methods: Plasma circRNA expression profiles were screened by circRNA microarrays and verified by qRT-PCR method. CircRNA–miRNA–mRNA network was established to predict the circRNA targets. Gene ontology (GO) analysis and KEGG pathway analysis were applied for further enrichment of mRNA data. Results: CircRNA microarrays study identified 13 downregulated and 46 upregulated circRNAs in hypertension patients, where four circRNAs (hsa-circ-0000437, hsa-circ-0008139, hsa-circ-0005870 and hsa-circ-0040809) showed significantly difference. By further validation, hsa-circ-0005870 exhibited significant downregulation in hypertensive patients. Then, we constructed a network of hsa-circ-0005870-targeted miRNAs, including hsa-miR-6807-3p, hsa-miR-5095, hsa-miR-1273g-3p, hsa-miR-5096, hsa-miR-619-5p, and their corresponding mRNAs. Gene oncology and KEGG pathway analysis enriched from specific mRNAs indicated the involvement of hsa-circ-0005870 in hypertension. Conclusions: In summary, hsa-circ-0005870 may represent a novel biomarker for the diagnosis of hypertension, and hsa-circ-0005870-miRNA-mRNA network may provide potential mechanism for hypertension.     

HOXB13 facilitates hepatocellular carcinoma progression by activating AKT/mTOR signaling pathway

Introduction and ObjectivesHepatocellular carcinoma (HCC) is one of the sixth most common malignancies worldwide and is accompanied by high mortality. Homeobox B13 (HOXB13) has been shown to be involved in the development of various cancers. This study aimed to investigate the role of HOXB13 in HCC progression.Materials and MethodsThe expression of HOXB13 in HCC tumor tissues was analyzed using qRT-PCR and immunohistochemical staining . After overexpression or downregulation of HOXB13 in HCC cell lines, cell proliferation was detected by CCK8 assay and Ki67 staining and cell invasion ability were tested by transwell assay. Western blot assay was applied to analyze the effect of HOXB13 on related signaling pathways. In addition, the role of HOXB13 on HCC in vivo was explored using a HCC mouse model. IF and WB were performed to detect cell proliferation, apoptosis and related protein expression in mice tumor tissues.ResultsThe results showed that the expression of HOXB13 was significantly increased in HCC tissues compared with adjacent tissues and positively correlated with the tumor stage and survival of HCC patients. Overexpression of HOXB13 promoted the proliferation and invasion of HCC cells and up-regulated the protein expression of AKT, mTOR and MMP2. In contrast, the downregulation of HOXB13 resulted in the opposite results. In vivo experiments, HOXB13 significantly promoted tumor growth in mice bearing HCC by promoting cell proliferation and inhibiting cell apoptosis.ConclusionsThis study suggested that HOXB13 can facilitate HCC progression by activation of the AKT/mTOR signaling pathway. HOXB13 may be a novel target for HCC therapy.     

Circ_0000291 contributes to hepatocellular carcinoma tumorigenesis by binding to miR-1322 to up-regulate UBE2T

Background and objectivesCircular RNAs (circRNAs) are identified to show important regulatory functions in cancer biology. We attempted to analyze the role of circ_0000291 in hepatocellular carcinoma (HCC) progression and its related mechanism.MethodsThe circular characteristic of circ_0000291 was tested using exonuclease RNase R. Cell proliferation was analyzed by 5-Ethynyl-2’-deoxyuridine (EdU) incorporation and colony formation assays. Cell apoptosis was measured by flow cytometry and a caspase 3 activity assay kit. Transwell assays were performed to analyze cell migration and invasion abilities. Sphere formation assay was conducted to analyze cell stemness. Dual-luciferase reporter and RNA-pull down assays were conducted to verify the interaction between microRNA-1322 (miR-1322) and circ_0000291 or ubiquitin conjugating enzyme E2 T (UBE2T).ResultsCirc_0000291 was markedly up-regulated in HCC tissues and cell lines. HCC patients with high expression of circ_0000291 displayed a low survival rate. Circ_0000291 knockdown restrained the proliferation, migration, invasion, and stemness and induced the apoptosis of HCC cells. Circ_0000291 directly interacted with miR-1322 and negatively regulated miR-1322 expression. Circ_0000291 knockdown-mediated anti-tumor impacts in HCC cells were largely overturned by the interference of miR-1322. miR-1322 directly paired with the 3’ untranslated region (3’UTR) of UBE2T, and UBE2T was negatively regulated by miR-1322. UBE2T overexpression largely reversed circ_0000291 silencing-induced effects in HCC cells. Circ_0000291 positively regulated UBE2T expression by absorbing miR-1322 in HCC cells. Circ_0000291 silencing notably reduced the tumorigenic potential in vivo.ConclusionCirc_0000291 facilitated HCC progression by targeting miR-1322/UBE2T axis, which provided novel potential biomarkers and targets for HCC patients.     

Tumor-derived extracellular vesicles containing long noncoding RNA PART1 exert oncogenic effect in hepatocellular carcinoma by polarizing macrophages into M2

AimWe explored whether tumor-derived extracellular vesicles (EVs) could deliver long noncoding RNA (lncRNA) PART1 into macrophage to orchestrate macrophage polarization in the progression of hepatocellular carcinoma (HCC).MethodThe expression patterns of PART1, microRNA (miR)-372-3p and TLR4 were detected by RT-qPCR in the HCC tissues and HCC cells. PART1 was silenced or overexpressed in HCC cells to assess its effects on the HCC cell process. EVs were isolated from PART1-overexpressed HCC cells, and co-cultured with macrophages, and gain- and loss-of-function assays were implemented in macrophages to evaluate their role in macrophage polarization. Relationship among PART1, miR-372-3p, and TLR4 was evaluated. Effect of EV-PART1 on tumorigenicity in vivo was detected by subcutaneous tumorigenicity test in nude mice.ResultPART1 and TLR4 were upregulated while miR-372-3p was downregulated in HCC tissues and cells. PART1 increased HCC cell proliferation, migration, invasion, and EMT. Mechanistically, PART1 bound to miR-372-3p to downregulate its expression, whereas TLR4 was negatively targeted by miR-372-3p in the macrophages. EVs containing PART1, TLR4 overexpression, or miR-372-3p inhibition induced M2 polarization of macrophages. Also, EVs containing PART1 promoted M2 polarization of macrophages and the occurrence of HCC by affecting miR-372-3p/TLR4 axis.ConclusionHCC cell-derived EVs might up-regulate TLR4 by inhibiting miR-372-3p via PART1 delivery to promote macrophage M2 polarization in HCC.     

Long non-coding ribonucleic acid W5 inhibits progression and predicts favorable prognosis in hepatocellular carcinoma

BACKGROUNDAccumulating evidence has revealed that several long non-coding ribonucleic acids (lncRNAs) are crucial in the progress of hepatocellular carcinoma (HCC).AIMTo classify a long non-coding RNA, i.e., lncRNA W5, and to determine the clinical significance and potential roles of lncRNA W5 in HCC.METHODSThe results showed that lncRNA W5 expression was significantly downregulated in HCC cell lines and tissues. Analysis of the association between lncRNA W5 expression levels and clinicopathological features suggested that low lncRNA W5 expression was related to large tumor size (P < 0.01), poor histological grade (P < 0.05) and serious portal vein tumor thrombosis (P < 0.05). Furthermore, Kaplan-Meier survival analysis showed that low expression of lncRNA W5 predicts poor overall survival (P = 0.016).RESULTSGain-of-loss function experiments, including cell counting kit8 assays, colony formation assays, and transwell assays, were performed in vitro to investigate the biological roles of lncRNA W5. In vitro experiments showed that ectopic overexpression of lncRNA W5 suppressed HCC cell proliferation, migration and invasion; conversely, silencing of lncRNA W5 promoted cell proliferation, migration and invasion. In addition, acting as a tumor suppressor gene in HCC, lncRNA W5 inhibited the growth of HCC xenograft tumors in vivo.CONCLUSIONThese results showed that lncRNA W5 is down-regulated in HCC, and it may suppress HCC progression and predict poor clinical outcomes in patients with HCC. LncRNA W5 may serve as a potential HCC prognostic biomarker in addition to a therapeutic target.     

STAM binding protein regulated by hsa_circ_0007334 exerts oncogenic potential in pancreatic cancer

BackgroundPancreatic cancer (PC) is a highly aggressive and metastatic malignancy. The molecular events related to PC have not yet been fully elucidated. The STAM binding protein (STAMBP), a deubiquitinase, contributes to carcinogenesis in several types of cancer. Our study aims to investigate the function of STAMBP in the progression of PC.MethodsFifteen pairs of tumor and tumor-adjacent tissues were obtained from PC patients. Human pancreatic cancer cell lines, SW 1990 and BxPC-3, were transfected with short hairpin RNA targeting STAMBP or/and vectors overexpressing wild-type STAMBP or STAMBP D348A mutants (inactive mutants of STAMBP). SW 1990 cells were co-transfected with vectors overexpressing STAMBP and small interfering RNA targeting hsa_circ_0007334.ResultsSTAMBP was overexpressed in the tumor tissues as compared with the tumor-adjacent tissues from PC patients. Higher STAMBP expression in the tumor tissues showed worse prognosis. Loss/gain-of-function experiments revealed that STAMBP promoted the malignant behaviors of PC cells in vitro and xenograft tumor growth in vivo. Activation of NF-κB in PC cells was triggered by STAMBP. However, inactive mutants of STAMBP lost these biological functions in PC. hsa_circ_0007334, an oncogene in PC progression, was found to up-regulate STAMBP expression in PC cells. STAMBP up-regulation reversed the effects of hsa_circ_0007334 silencing on cell mobility.ConclusionsThese results indicated that STAMBP depended on its deubiquitinase activities to induce the malignant behaviors of PC cells and was involved in the regulatory mechanism of hsa_circ_0007334 on PC cell mobility. Our findings provide a novel insight into the molecular mechanism of PC.     

Circ-LARP1B knockdown restrains the tumorigenicity and enhances radiosensitivity by regulating miR-578/IGF1R axis in hepatocellular carcinoma

Introduction and ObjectivesCircular RNA La Ribonucleoprotein 1B (circ-LARP1B) was reported to serve as an oncogene in many types of cancers. Radiotherapy (RT) is an important element of the multimodal treatment concept in malignancies. Here, this work aimed to investigate the role of circ-LARP1B in the tumorigenesis and radiosensitivity of hepatocellular carcinoma (HCC).Patients or Materials and MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of genes and proteins. In vitro experiments were conducted using cell counting Kit-8 (CCK-8), colony formation, EDU, transwell, and tube formation assays, respectively. Dual-luciferase reporter assay was employed to identify the target relationship between miR-578 and circ-LARP1B or IGF1R (insulin-like growth factor 1 receptor). In vivo assay was performed using murine xenograft model.ResultsCirc-LARP1B was highly expressed in HCC tissues and cells, and high expression of circ-LARP1B was closely associated with poor prognosis. Functional experiments demonstrated that circ-LARP1B silencing impaired cell proliferation, invasion, angiogenesis and reduced radioresistance in vitro. Mechanistically, circ-LARP1B could competitively bind with miR-578 to relieve the repression of miR-578 on the expression of its target gene IGF1R. Further rescue assay confirmed that miR-578 inhibition reversed the inhibitory effects of circ-LARP1B knockdown on HCC cell malignant phenotypes and radioresistance. Moreover, miR-578 overexpression restrained tumorigenicity and enhanced radiosensitivity in HCC cells, which were attenuated by IGF1R up-regulation. Besides that, circ-LARP1B knockdown impeded tumor growth and enhanced irradiation sensitivity in HCC in vivo.ConclusionsCirc-LARP1B knockdown restrained HCC tumorigenicity and enhanced radiosensitivity by regulating miR-578/IGF1R axis, providing a new target for the treatment of HCC.