RBM15 promotes hepatocellular carcinoma progression by regulating N6-methyladenosine modification of YES1 mRNA in an IGF2BP1-dependent manner

AbstractThe function of the N6-methyladenosine (m6A) methyltransferase RNA-binding motif protein 15 (RBM15) in hepatocellular carcinoma (HCC) has not been thoroughly investigated. Here we determined the clinical value, biological functions, and potential mechanisms of RBM15 in HCC. Expression of RBM15 was identified using tissue microarrays and online databases. A risk-prediction model based on RBM15 was developed and validated. We determined the biological role of RBM15 on HCC cells in vitro and in vivo. RNA sequencing was used to screen candidate targets of RBM15. Subsequently, the m6A dot blot assay, methylated RNA immunoprecipitation qPCR, dual-luciferase reporter assays, RNA decay assay, and RNA immunoprecipitation qPCR were employed to explore the mechanisms of RBM15. Our study showed that RBM15 was highly expressed in HCC, and overexpression of RBM15 indicated a worse outcome. A new nomogram combining RBM15 with age and TNM stage was developed and validated to predict the outcome of HCC patients; our nomogram increased the prediction accuracy of the TNM system. Functionally, RBM15 facilitates the proliferation and invasiveness of HCC. RBM15-mediated m6A modification contributed to a post-transcriptional activation of YES proto-oncogene 1 (YES1) in an insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)-dependent manner. In addition, YES1 was confirmed as an oncogene in HCC cells by activating the mitogen-activated protein kinase (MAPK) pathway. In conclusion, RBM15-mediated m6A modification might facilitate the progression of HCC via the IGF2BP1–YES1–MAPK axis. RBM15 may be a promising biomarker in the outcome prediction of HCC.

Download Full-text

Epigenetic regulation of ferroptosis via ETS1/miR-23a-3p/ACSL4 axis mediates sorafenib resistance in human hepatocellular carcinoma

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02208-x ◽

2022 ◽

Vol 41 (1) ◽

Author(s):

Yuanjun Lu ◽

Yau-Tuen Chan ◽

Hor-Yue Tan ◽

Cheng Zhang ◽

Wei Guo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Drug Resistance ◽

Molecular Mechanisms ◽

Luciferase Reporter ◽

Dependent Manner ◽

Bioinformatics Analyses ◽

Sorafenib Treatment ◽

Hcc Cells

Abstract Background Drug resistance to sorafenib greatly limited the benefits of treatment in patients with hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) participate in the development of drug resistance. The key miRNA regulators related to the clinical outcome of sorafenib treatment and their molecular mechanisms remain to be identified. Methods The clinical significance of miRNA-related epigenetic changes in sorafenib-resistant HCC was evaluated by analyzing publicly available databases and in-house human HCC tissues. The biological functions of miR-23a-3p were investigated both in vitro and in vivo. Proteomics and bioinformatics analyses were conducted to identify the mechanisms that regulating miR-23a-3p. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were used to validate the binding relationship of miR-23a-3p and its targets. Results We found that miR-23a-3p was the most prominent miRNA in HCC, which was overexpressed in sorafenib non-responders and indicated poor survival and HCC relapse. Sorafenib-resistant cells exhibited increased miR-23a-3p transcription in an ETS Proto-Oncogene 1 (ETS1)-dependent manner. CRISPR-Cas9 knockout of miR-23a-3p improved sorafenib response in HCC cells as well as orthotopic HCC tumours. Proteomics analysis suggested that sorafenib-induced ferroptosis was the key pathway suppressed by miR-23a-3p with reduced cellular iron accumulation and lipid peroxidation. MiR-23a-3p directly targeted the 3′-untranslated regions (UTR) of ACSL4, the key positive regulator of ferroptosis. The miR-23a-3p inhibitor rescued ACSL4 expression and induced ferrotoptic cell death in sorafenib-treated HCC cells. The co-delivery of ACSL4 siRNA and miR-23a-3p inhibitor abolished sorafenib response. Conclusion Our study demonstrates that ETS1/miR-23a-3p/ACSL4 axis contributes to sorafenib resistance in HCC through regulating ferroptosis. Our findings suggest that miR-23a-3p could be a potential target to improve sorafenib responsiveness in HCC patients.

Download Full-text

CircRNA LRIG3 knockdown inhibits hepatocellular carcinoma progression by regulating miR-223-3p and MAPK/ERK pathway

Archives of Medical Science ◽

10.5114/aoms/124975 ◽

2021 ◽

Author(s):

Hui Sun ◽

Junwei Zhai ◽

Li Zhang ◽

Yingnan Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Protein Kinase ◽

Molecular Mechanisms ◽

Mitogen Activated Protein Kinase ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Erk Pathway ◽

Mitogen Activated Protein ◽

Hcc Cells

IntroductionEmerging evidence suggests that circular RNAs (circRNAs) play critical roles in tumorigenesis. However, the roles and molecular mechanisms of circRNA leucine-rich repeat immunoglobulin domain-containing protein 3 (circ_LRIG3) in hepatocellular carcinoma (HCC) has not been investigated.Material and methodsThe expression levels of circ_LRIG3, miR-223-3p, and mitogen-activated protein kinase kinase 6 (MAP2K6) were determined by qRT-PCR. Flow cytometry was applied to determine the cell cycle distribution and apoptosis. Cell proliferation, migration and invasion were assessed by MTT, colony formation, and transwell assays. Western blot assay was employed to measure the protein levels of the snail, E-cadherin, MAP2K6, mitogen-activated protein kinase (MAPK), phospho-MAPK (p-MAPK), extracellular signal-regulated kinases (ERKs), and phospho-ERKs (p- ERKs). The relationship between miR-223-3p and circ_LRIG3 or MAP2K6 was predicted by bioinformatics tools and verified by dual-luciferase reporter assay. A xenograft tumor model was established to confirm the functions of circ_LRIG3 in vivo.ResultsCirc_LRIG3 and MAP2K6 expression were enhanced while miR-223-3p abundance was reduced in HCC tissues and cells. Knockdown of circ_LRIG3 inhibited cell proliferation, metastasis, and increasing apoptosis. MiR-223-3p was a target of circ_LRIG3, and its downregulation reversed the inhibitory effect of circ_LRIG3 knockdown on the progression of HCC cells. Moreover, MAP2K6 could bind to miR-223-3p, and MAP2K6 upregulation also abolished the suppressive impact of circ_LRIG3 interference on progression of HCC cells. Additionally, the silence of circ_LRIG3 suppressed the activation of the MAPK/ERK pathway and tumor growth by upregulating miR-223-3p and downregulating MAP2K6.ConclusionsCirc_LRIG3 knockdown inhibited HCC progression through regulating miR-223-3p/MAP2K6 axis and inactivating MAPK/ERK pathway.

Download Full-text

Exosomal hsa_circ_0004658 derived from RBPJ overexpressed-macrophages inhibits hepatocellular carcinoma progression via miR-499b-5p/JAM3

Cell Death and Disease ◽

10.1038/s41419-021-04345-9 ◽

2022 ◽

Vol 13 (1) ◽

Author(s):

Lei Zhang ◽

Jing Zhang ◽

Pengfei Li ◽

Ting Li ◽

Zhiqin Zhou ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Xenograft Model ◽

Circular Rna ◽

Luciferase Reporter ◽

Mouse Xenograft Model ◽

Rna Immunoprecipitation ◽

And Migration ◽

Hcc Cells

AbstractMacrophage-derived exosomes (Mφ-Exo) have multidimensional involvement in tumor initiation, progression, and metastasis, but their regulation in hepatocellular carcinoma (HCC) is not fully understood. RBPJ has been implicated in macrophage activation and plasticity. In this study we assess the role of exosomes derived from RBPJ-overexpressed macrophages (RBPJ+/+ Mφ-Exo) in HCC. The circular RNA (circRNA) profiles in RBPJ+/+ Mφ-Exo and THP-1-like macrophages (WT Mφ)-Exo was evaluated using circRNA microarray. CCK-8, Transwell, and flow cytometry analyses were used to evaluate the function of Mφ-Exo-circRNA on HCC cells. Luciferase reporter assays, RNA immunoprecipitation, and Pearson’s correlation analysis were used to confirm interactions. A nude mouse xenograft model was used to further analyze the functional significance of Mφ-Exo-cirRNA in vivo. Our results shown that hsa_circ_0004658 is upregulated in RBPJ+/+ Mφ-Exo compared to WT Mφ-Exo. RBPJ+/+ Mφ-Exo and hsa_circ_0004658 inhibits proliferation and promotes apoptosis in HCC cells, whereas hsa_circ_0004658 knockdown stimulated cell proliferation and migration but restrained apoptosis in vitro and promotes tumor growth in vivo. The effects of RBPJ+/+ Mφ-Exo on HCC cells can be reversed by the hsa_circ_0004658 knockdown. Mechanistic investigations revealed that hsa_circ_0004658 acts as a ceRNA of miR-499b-5p, resulting in the de-repression of JAM3. These results indicate that exosome circRNAs secreted from RBPJ+/+ Mφ inhibits tumor progression through the hsa_circ_0004658/miR-499b-5p/JAM3 pathway and hsa_circ_0004658 may be a diagnostic biomarker and potential target for HCC therapy.

Download Full-text

Circ_0004913 Sponges miR-1290 and Regulates FOXC1 to Inhibit the Proliferation of Hepatocellular Carcinoma

10.21203/rs.3.rs-36547/v1 ◽

2020 ◽

Author(s):

Yabin Yu ◽

Suyang Han ◽

Meng Li ◽

Yan Song ◽

Fuzhen Qi

Keyword(s):

Hepatocellular Carcinoma ◽

Circular Rna ◽

Gene Expression Omnibus ◽

Luciferase Reporter ◽

Luciferase Reporter Gene ◽

Reverse Transcription Pcr ◽

Gene Assay ◽

Rna Immunoprecipitation ◽

Malignant Behavior ◽

Hcc Cells

Abstract Background Circular RNA (circRNA), a novel type of non-coding RNA, could interact with miRNA and protein molecules to regulate the occurrence and progression of hepatocellular carcinoma (HCC). However, little is known about the pathogenesis of circ_0004913 in HCC.Materials Through the GEO (Gene Expression Omnibus database) to find dysfunctional circRNAs in HCC, and circ_0004913 was selected as the research object. Quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression level of circ_0067934 in HCC tissues and cells. CCK-8, Edu and flow cytometry assays were chosed to determine the malignant behavior of transfected HCC cells. Mechanistically, RNA immunoprecipitation and dual-luciferase reporter gene assay were performed to explore the relation between circ_0067934, miR-1290 and FOXC1 (Forkhead box C1) in HCC.Results The expression of circ_0004913 was down-regulated in HCC tissues and cell lines, while the overexpression of circ_0004913 attenuates the malignant behavior of HCC cells. Bioinformatics predicted that circ_0004913 interacts with miR-1290, which targeted FOXC1 mRNA. In fact, miR-1290 promoted the malignant behavior of HCC cells, while FOXC1 had the opposite effect. In addition, circ_0004913 overexpression enhanced FOXC1 expression by reducing miR-1290 expression, thereby inhibiting the proliferation of HCC cells.Conclusion Circ_0004913 / miR-1290 / FOXC1 regulatory axis could inhibit the progress of HCC. Our findings may provide potential new targets for the diagnosis and treatment of HCC.

Download Full-text

CircRNA hsa_circ_0110102 Function as Anti-Oncogenic Gene in Hepatocellular Carcinoma Through Modulating miR-580-5p/CCL2 Pathway

10.21203/rs.3.rs-62221/v1 ◽

2020 ◽

Author(s):

Xinxing Wang ◽

Wei Sheng ◽

Tao Xu ◽

Jiawen Xu ◽

Zhenhai Zhang

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Lines ◽

Molecular Mechanisms ◽

Luciferase Assay ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Dependent Manner ◽

Expression Levels ◽

Cox 2 ◽

Hcc Cells

Abstract Background: Circular RNAs (circRNAs) have been shown to have critical regulatory roles in tumor biology, whereas their contributions in hepatocellular carcinoma (HCC) still remains enigmatic. The purpose of this study was to investigate the molecular mechanisms involved in hsa_circ_0110102 in the occurrence and development of HCC. Methods: The expression levels of hsa_circ_0110102 in HCC cell lines and tissues were estimated by RT-qPCR assay. The proliferation, migration, and invasion of HCC cells were determined by CCK-8 and transwell assay. The western blot and ELISA were employed to examine the related-protein and cytokine expression. The association between miR-580-5p and hsa_circ_0110102 or CCL2 was predicted and affirmed by dual-luciferase reporter assay and RNA pull-down.Results: hsa_circ_0110102 was significantly down-regulated in HCC cell lines and tissues, low hsa_circ_0110102 expression levels were associated with poor prognosis. Knockdown hsa_circ_0110102 significantly inhibited cell proliferation, migration and invasion. In addition, luciferase assay and RNA pull-down assay indicating that hsa_circ_0110102 function as sponge for miR-580-5p. Moreover, miR-580-5p which could directly bind to the 3’-UTR of CCL2 and induce its expression, then active the COX-2/PGE2 pathway in macrophage via FoxO1 in p38 MAPK dependent manner. Furthermore, the Δ256 mutant of FoxO1 showed no activation effect. Conclusion: hsa_circ_0110102 act as a sponge for miR-580-5p and decreased CCL2 secretion in HCC cells, then inhibits pro-inflammatory cytokine release from activated macrophage by regulating the COX-2/PGE2 pathway. These results indicating that hsa_circ_0110102 serves as a potential prognostic predictor or therapeutic target for HCC.

Download Full-text

HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-020-00453-8 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Qing Li ◽

Yong Ni ◽

Liren Zhang ◽

Runqiu Jiang ◽

Jing Xu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chromatin Immunoprecipitation ◽

Cox Regression ◽

Luciferase Reporter ◽

Dependent Manner ◽

Cox Regression Analysis ◽

Polysome Profiling ◽

Rna Immunoprecipitation ◽

Reporter Assays

AbstractN6-methyladenosine (m6A), and its reader protein YTHDF1, play a pivotal role in human tumorigenesis by affecting nearly every stage of RNA metabolism. Autophagy activation is one of the ways by which cancer cells survive hypoxia. However, the possible involvement of m6A modification of mRNA in hypoxia-induced autophagy was unexplored in human hepatocellular carcinoma (HCC). In this study, specific variations in YTHDF1 expression were detected in YTHDF1-overexpressing, -knockout, and -knockdown HCC cells, HCC organoids, and HCC patient-derived xenograft (PDX) murine models. YTHDF1 expression and hypoxia-induced autophagy were significantly correlated in vitro; significant overexpression of YTHDF1 in HCC tissues was associated with poor prognosis. Multivariate cox regression analysis identified YTHDF1 expression as an independent prognostic factor in patients with HCC. Multiple HCC models confirmed that YTHDF1 deficiency inhibited HCC autophagy, growth, and metastasis. Luciferase reporter assays and chromatin immunoprecipitation demonstrated that HIF-1α regulated YTHDF1 transcription by directly binding to its promoter region under hypoxia. The results of methylated RNA immunoprecipitation sequencing, proteomics, and polysome profiling indicated that YTHDF1 contributed to the translation of autophagy-related genes ATG2A and ATG14 by binding to m6A-modified ATG2A and ATG14 mRNA, thus facilitating autophagy and autophagy-related malignancy of HCC. Taken together, HIF-1α-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related HCC progression via promoting translation of autophagy-related genes ATG2A and ATG14 in a m6A-dependent manner. Our findings suggest that YTHDF1 is a potential prognostic biomarker and therapeutic target for patients with HCC.

Download Full-text

Asparagus Polysaccharide Suppresses the Migration, Invasion, and Angiogenesis of Hepatocellular Carcinoma Cells Partly by Targeting the HIF-1α/VEGF Signalling Pathway In Vitro

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/3769879 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Wei Cheng ◽

Ziwei Cheng ◽

Dongwei Xing ◽

Minguang Zhang

Keyword(s):

Hepatocellular Carcinoma ◽

Transcriptional Activation ◽

Umbilical Vein ◽

Signalling Pathway ◽

Migration And Invasion ◽

Dependent Manner ◽

Antitumor Effects ◽

Vegf Signalling ◽

Hcc Cells

Hypoxia-inducible factor-1α (HIF-1α) plays a key role by triggering the transcriptional activation of a number of genes involved in migration, invasion, and angiogenesis in hepatocellular carcinoma (HCC). Thus, suppressing tumour growth by targeting the HIF-1α/VEGF signalling pathway represents a promising strategy for the treatment of HCC. In our previous studies, we found that asparagus polysaccharide (ASP) suppressed the proliferation and promoted the apoptosis of HCC cells both in vivo and in vitro. To further explore the potential mechanisms of the antitumor effects of ASP in HCC, we investigated effects of ASP on the migration, invasion, and angiogenesis of HCC cells (SK-Hep1 and Hep-3B) using an in vitro experimental model. First, we found that ASP effectively suppressed the proliferation of the SK-Hep1 and Hep-3B cells but did not cause significant cytotoxicity in normal liver cells (L-O2). Then, we found that ASP inhibited the migration and invasion of the SK-Hep1 and Hep-3B cells and HCC cells-induced angiogenesis of human umbilical vein endothelial cells in a concentration-dependent manner. Mechanistic studies revealed that the inhibition of migration, invasion, and angiogenesis by ASP in the SK-Hep1 and Hep-3B cells might occur via the downregulation of HIF-1α/VEGF signalling pathway. Finally, our results also showed that the inhibition of HIF-1α by ASP may be mediated through the downregulation of the phosphorylation levels of AKT, mTOR, and ERK. In conclusion, our results suggest that ASP suppresses the migration, invasion, and angiogenesis of HCC cells partly via inhibiting the HIF-1α/VEGF signalling pathway.

Download Full-text

CircRNA LRIG3 knockdown inhibits the progression of hepatocellular carcinoma by regulating miR-223-3p/MAP2K6 axis and inactivating MAPK/ERK pathway

10.21203/rs.3.rs-17512/v1 ◽

2020 ◽

Author(s):

Hui Sun ◽

Junwei Zhai ◽

Li Zhang ◽

Yingnan Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Protein Kinase ◽

Mitogen Activated Protein Kinase ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Cell Cycle Distribution ◽

Erk Pathway ◽

Mitogen Activated Protein ◽

Hcc Cells

Abstract Background: Emerging evidence suggests that circular RNAs (circRNAs) play critical roles in tumorigenesis. However, the roles and molecular mechanism of circRNA leucine-rich repeat immunoglobulin domain-containing protein 3 (circ_LRIG3) in hepatocellular carcinoma (HCC) have not been investigated.Methods: The expression levels of circ_LRIG3, microRNA-223-3p (miR-223-3p), and mitogen-activated protein kinase kinase 6 (MAP2K6) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was applied to determine the cell cycle distribution and cell apoptosis. Cell proliferation, migration and invasion were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and transwell assay, respectively. Western blot assay was employed to measure the protein levels of snail, E-cadherin, MAP2K6, mitogen-activated protein kinase (MAPK), phospho-MAPK (p-MAPK), extracellular signal-regulated kinases (ERKs), and phospho-ERKs (p-ERKs). The relationship between miR-223-3p and circ_LRIG3 or MAP2K6 was predicted by bioinformatics tools and verified by dual-luciferase reporter assay. A xenograft tumor model was established to confirm the functions of circ_LRIG3 in vivo.Results: Circ_LRIG3 and MAP2K6 expression were enhanced while miR-223-3p abundance was reduced in HCC tissues and cells. Knockdown of circ_LRIG3 inhibited the progression of HCC cells via reducing cell proliferation, metastasis and increasing apoptosis. MiR-223-3p was a target of circ_LRIG3 and its downregulation reversed the inhibitory effect of circ_LRIG3 knockdown on progression of HCC cells. Moreover, MAP2K6 could bind to miR-223-3p, and MAP2K6 upregulation also abolished the suppressive impact of circ_LRIG3 interference on progression of HCC cells. Additionally, silence of circ_LRIG3 suppressed the activation of MAPK/ERK pathway and tumor growth by upregulating miR-223-3p and downregulating MAP2K6.Conclusion: Circ_LRIG3 knockdown inhibited HCC progression through regulating miR-223-3p/MAP2K6 axis and inactivating MAPK/ERK pathway, providing a potential therapeutic approach for patients with HCC.

Download Full-text

DLG1-AS1 is activated by MYC and drives the proliferation and migration of hepatocellular carcinoma cells through miR-497-5p/SSRP1 axis

Cancer Cell International ◽

10.1186/s12935-020-01667-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jie Min ◽

Dayong Jin ◽

Feng Zhang ◽

Yanxia Kang ◽

Yuhong Qi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transcriptional Activation ◽

Underlying Mechanism ◽

Carcinoma Cells ◽

Luciferase Reporter ◽

Cell Growth And Migration ◽

Cellular Processes ◽

And Migration ◽

Rip Assay ◽

Hcc Cells

Abstract Background Long non-coding RNAs (lncRNAs) have been reported to be biological regulators in hepatocellular carcinoma (HCC). DLG1 antisense RNA 1 (DLG1-AS1) has been found to be up-regulated in cervical cancer. However, its function and underlying mechanism in HCC remains unknown. Methods DLG1-AS1 expression was assessed in HCC cells and normal cell by RT-qPCR. Luciferase reporter assay, RNA pull down assay and RIP assay were used to demonstrate the interaction between DLG1-AS1 and miR-497-5p. Results DLG1-AS1 was highly expressed in HCC cells. Silencing of DLG1-AS1 led to the inhibition of HCC cell growth and migration. Besides, MYC induced the transcriptional activation of DLG1-AS1. MYC could facilitate HCC cellular processes by up-regulating DLG1-AS1. MiR-497-5p could interact with DLG1-AS1 in HCC cells. Down-regulation of miR-497-5p could reverse the impacts of DLG1-AS1 silencing on HCC cells. SSRP1 expression could be positively regulated by DLG1-AS1 but was negatively regulated by miR-497-5p. Knockdown of DLG1-AS1 suppressed tumor growth in nude mice. Conclusions DLG1-AS1 is activated by MYC and functions as an oncogene in HCC via miR-497-5p/SSRP1 axis.

Download Full-text

Propofol suppresses cell viability, cell cycle progression and motility and induces cell apoptosis of ovarian cancer cells through suppressing MEK/ERK signaling via targeting circVPS13C/miR-145 axis

Journal of Ovarian Research ◽

10.1186/s13048-021-00775-3 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Huan Lu ◽

Guanlin Zheng ◽

Xiang Gao ◽

Chanjuan Chen ◽

Min Zhou ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cancer Cells ◽

Rna Binding ◽

Erk Signaling ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Vacuolar Protein

Abstract Background Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. Methods The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. Results Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. Conclusion Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro.

Download Full-text