Circ_LDLR Knockdown Suppresses Progression of Hepatocellular Carcinoma via Modulating miR-7/RNF38 Axis

Jia, Yuming; Li, Shengchao; Zhang, Meng; Zhang, Zhilei; Wang, Chao; Zhang, Chong; Yang, Wuhan; Peng, Li; Xu, Zhuo

doi:10.2147/cmar.s275003

Cited by 8 publications

(7 citation statements)

References 34 publications

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“…We found that the anti-tumor effects mediated by miR-568 in HCC cells could be largely overturned by the overexpression of RNF38, suggesting that miR-568 hampered HCC development by down-regulating RNF38. The oncogenic role of RNF38 was consistent with the previous study (20). Circ_0097009 could up-regulate RNF38 expression by sponging miR-568 in HCC cells.…”

Section: Discussionsupporting

confidence: 90%

“…For instance, Wu et al reported that RNF38 elevated the cisplatin resistance of non-small cell lung cancer cells (33). In HCC, Jia et al suggested that RNF38, targeted by miR-7, could reinforce HCC cell proliferation and metastasis (20), suggesting the oncogenic role of RNF38 in HCC. We found that the anti-tumor effects mediated by miR-568 in HCC cells could be largely overturned by the overexpression of RNF38, suggesting that miR-568 hampered HCC development by down-regulating RNF38.…”

Section: Discussionmentioning

confidence: 99%

“…Ring fi nger protein 38 (RNF38), a member of the ubiquitin ligase family with RING domain, was involved in the pathological process of several diseases, including HCC (16)(17)(18)(19). Previous studies have claimed that RNF38 could be targeted by miR-7 (20). The interaction between miR-568 and RNF38 has never been reported.…”

Section: Introductionmentioning

confidence: 99%

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Hsa_circ_0097009 regulates proliferation, apoptosis, migration and invasion of hepatocellular carcinoma cells via miR-568/RNF38 axis

Wu¹,

Li²,

Liu³

et al. 2023

BLL

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BACKGROUND: Circular RNAs (circRNAs), a class of non-coding RNAs, has been proved as an essential driver of hepatocellular carcinoma (HCC) progression. However, the aim of this study is to explore the role of hsa_circ_0097009 (circ_0097009) in HCC progression. METHODS: Ki67 expression in HCC tissues was labeled and examined by IHC assay. Quantitative real-time PCR (qRT-PCR) was applied to assess the expression of circ_0097009, miR-568 and RING fi nger protein 38 (RNF38). Western blot assay was conducted to analyze protein expression. HCC cell colony formation, proliferation, migration, invasion, angiogenesis ability and apoptosis were determined by colony formation assay, 5-ethynyl-29-deoxyuridine (EdU) assay, wound healing assay, trans well assay, angiogenesis assay and fl ow cytometry. The interaction between circ_0097009 and miR-568 as well as miR-568 and RNF38 was probed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: We found that circ_0097009 and RNF38 expressions were markedly higher, but miR-568 expression was signifi cantly lower in HCC. Circ_0097009 knockdown blocked HCC cell cloning, proliferation, migration, invasion, angiogenesis and facilitated apoptosis. MiR-568 was a target of circ_0097009 in HCC cells. MiR-568 interference could attenuate the circ_0097009 knockdown-induced inhibition on HCC cells progress. MiR-568 depressed cell clonal formation, proliferation, migration, invasion, angiogenesis and promotion of apoptosis, by targeting RNF38, and RNF38 overexpression reversed the suppression of miR-568 in HCC cells. Also, circ_0097009 knockdown blocked tumor growth in vivo CONCLUSION: Together, this study indicated that the oncogenic function of circ_0097009 in HCC, and circ_0097009/miR-568/RNF38 axis was expected to be a novel therapeutic option for HCC patients (Tab. 1, Fig. 7, Ref. 33).

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Hsa_circ_0097009 regulates proliferation, apoptosis, migration and invasion of hepatocellular carcinoma cells via miR-568/RNF38 axis

Wu¹,

Li²,

Liu³

et al. 2023

BLL

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“…Studies increasingly indicate that circRNAs rely on competitive endogenous RNAs (ceRNAs) to modulate the expression of downstream miRNAs [ 14 ]. In HCC, circPVT1 regulates cellular proliferation, apoptosis, and glycolysis via the miR-377/TRIM23 axis, and circLDLR knockdown suppresses HCC progression through the miR-7/RNF38 axis [ 15 , 16 ]. Moreover, miRNAs have been shown to regulate mRNA levels by targeting their 3′-untranslated regions (UTRs) [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Hsa_circ_0011385 knockdown represses cell proliferation in hepatocellular carcinoma

Yang

et al. 2021

Cell Death Discov.

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Circular RNAs (circRNAs), continuous loops of single-stranded RNA, regulate gene expression during the development of various cancers. However, the function of circRNAs in hepatocellular carcinoma (HCC) is rarely discussed. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the mRNA levels of circ_0011385, miR-361-3p, and STC2 in 96 pairs of HCC tissues (tumor tissues and adjacent normal tissues), HCC cell lines, and L02 (human normal liver cell line) cells. The relationships between circ_0011385 expression and clinical features of HCC were evaluated. Functional experiments in vitro or in vivo were used to evaluate the biological function of circ_0011385. Bioinformatics analysis was performed to predict miRNAs and mRNAs sponged by circ_0011385. RNA immunoprecipitation (RIP) and dual-luciferase reporter gene assays were used to elucidate the interactions among circ_0011385, miR-361-3p, and STC2 (stanniocalcin 2). ChIP and dual-luciferase reporter gene assays were used to identify the upstream regulator of circ_0011385. High expression of circ_0011385 was observed in HCC tissues and cell lines and was significantly associated with tumor size, TNM stage, and prognosis. In addition, inhibition of circ_0011385 expression prevented the proliferation of HCC cells in vitro and in vivo. Circ_0011385 sponged miR-361-3p, thereby regulating the mRNA expression of STC2. In addition, the transcription of circ_0011385 was regulated by SP3. Circ_0011385 knockdown suppressed cell proliferation and tumor activity in HCC. Circ_0011385 may therefore serve as a new biomarker in the diagnosis and treatment of HCC.

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“…In terms of HCC, the dysregulation of circRNAs has an inextricable correlation in the tumorigenesis and progression of the tumor [10,11]. For instance, Jia et al ., [12] reported that the upregulation of circ_LDLR could contribute to malignant behaviors of HCC cells by regulating RNF38 via miR-7. Synchronously, Luo et al ., [13] presented that circCAMSAP1 could aggravate HCC tumor progression by boosting cell proliferation, migration and invasion.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA circ_0073181 contributes to tumorigenesis by regulating protein tyrosine phosphatase receptor type E via miR-548p in hepatocellular carcinoma

Wang

Wang²,

Jia³

et al. 2021

Anti-Cancer Drugs

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Hepatocellular carcinoma (HCC) is a major world public problem in the world, with high morbidity and mortality rates. Circular RNA (circRNA) circ_0073181 has been reported to be related to HCC development. However, the mechanism of circ_0073181 in HCC is far from being addressed. Circ_0073181, microRNA-548p (miR-548p) and protein tyrosine phosphatase receptor type E (PTPRE) level were detected by real-time quantitative PCR (RT-qPCR). Cell proliferation, migration, invasion and apoptosis were detected by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine, wound healing, transwell and flow cytometry assay. Protein levels of proliferating cell nuclear antigen, Bcl-2 related X protein (Bax) and PTPRE were examined by western blot assay. The binding relationship between miR-548p and circ_0073181 or PTPRE was predicted by circular RNA interactome and targetScan and then verified by a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The biologic role of circ_0073181 on HCC tumor growth was examined by the xenograft tumor model in vivo. Circ_0073181 and PTPRE were upregulated, and miR-548p was decreased in HCC tissues and cells. Furthermore, circ_0073181 knockdown could boost proliferation, migration, invasion and repress apoptosis of HCC cells in vitro. The mechanical analysis suggested that circ_0073181 could regulate PTPRE expression by sponging miR-548p. In addition, circ_0073181 knockdown suppressed cell growth of HCC in vivo. Circ_0073181 silencing could inhibit HCC cell growth and metastasis partly by regulating the miR-548p/ PTPRE axis, providing a promising therapeutic target for the HCC treatment.

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Circ_LDLR Knockdown Suppresses Progression of Hepatocellular Carcinoma via Modulating miR-7/RNF38 Axis

Cited by 8 publications

References 34 publications

Hsa_circ_0097009 regulates proliferation, apoptosis, migration and invasion of hepatocellular carcinoma cells via miR-568/RNF38 axis

Hsa_circ_0097009 regulates proliferation, apoptosis, migration and invasion of hepatocellular carcinoma cells via miR-568/RNF38 axis

Hsa_circ_0011385 knockdown represses cell proliferation in hepatocellular carcinoma

Circular RNA circ_0073181 contributes to tumorigenesis by regulating protein tyrosine phosphatase receptor type E via miR-548p in hepatocellular carcinoma

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