CircBACH1 (hsa_circ_0061395) promotes hepatocellular carcinoma growth by regulating p27 repression via HuR

Liu, Bingqi; Yang, Guangsheng; Wang, Xin; Liu, Jingfang; Lu, Zhihua; Wang, Qi; Xu, Bing; Liu, Zhiqian; Li, Jie

doi:10.1002/jcp.29589

Cited by 67 publications

(64 citation statements)

References 47 publications

(32 reference statements)

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“…For instance, HuR has been reported to promote the progression of many cancers by enhancing the expression of multiple angiogenic factors [29]. Recent studies revealed that circRNAs may impair the stabilization and translation of mRNAs by competitively binding with HuR [30,31]. Consistently, in the present study, we proved that circDLC1 could reduce the interaction between HuR and MMP1 mRNA, therefore inhibit the expression of MMP1 and HCC progression.…”

Section: Discussionsupporting

confidence: 89%

“…HuR is the omnipresent member of the Hu/ELAV (human/embryonic lethal abnormal vision) RBP family and is responsible for the stabilization and (or) translation of many target mRNAs, which typically bear Urich 3 UTRs (27)(28)(29). Importantly, previous reports demonstrated that circRNA may impair the stabilization and translation of mRNAs by competitively binding with RNA-binding protein HuR (30,31). Thus, we hypothesized that circDLC1 may act as "sponges" for HuR, leading to decreased expressions of downstream target mRNA and protein.…”

Section: Circdlc1 Inhibited the Expression Of Mmp1 By Reducing The Inmentioning

confidence: 92%

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Circular RNA circDLC1 Inhibits MMP1-Mediated Liver Cancer Progression via Interaction with HuR

Liu

Lan

et al. 2020

Preprint

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Background: N6-methyladenosine (m6A) modification has been demonstrated to be closely related to cancer progression. KIAA1429, a key component of the m6A methyltransferase complex, has recently been reported to promote hepatocellular carcinoma (HCC) progression by regulating the m6A methylation. However, the involvement of circular RNAs (circRNAs) in KIAA1429-mediated HCC progression is still unknown.Methods: RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (m6A-seq) were utilized to identify KIAA1429-regulated circRNAs. The effects of circDLC1 on proliferation and metastasis of hepatoma cells were examined in vitro and in vivo. RT-qPCR was used to measure the expression of circDLC1 in HCC tissues and hepatoma cells. RNA FISH, RIP assays and biotin-labeled RNA pull-down were used to investigate the downstream effector of circDLC1. The downstream targets of circDLC1 were identified using RNA-seq.Results: Our data demonstrated that circDLC1 was downregulated in HCC tissues and closely relevant to favorable prognosis. Overexpression of circDLC1 inhibited the proliferation and motility of hepatoma cells in vitro and in vivo, while silencing of circDLC1 played the opposite role. Mechanistic investigations revealed that circDLC1 could bind to RNA-binding protein HuR, which subsequently reduced the interaction between HuR and MMP1 mRNAs, thus inhibited the expression of MMP1, finally contributed to inhibition of HCC progression.Conclusion: Our work suggests that circDLC1, a downstream target of KIAA1429, is a promising prognostic marker for HCC patients, and the circDLC1-HuR-MMP1 axis may serve as a potential therapeutic target for HCC treatment.

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Section: Discussionsupporting

confidence: 89%

Section: Circdlc1 Inhibited the Expression Of Mmp1 By Reducing The Inmentioning

confidence: 92%

Circular RNA circDLC1 Inhibits MMP1-Mediated Liver Cancer Progression via Interaction with HuR

Liu

Lan

et al. 2020

Preprint

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“…Total RNA was extracted using TRIzol reagent (#15596-026, Invitrogen), nuclear and cytoplasmic RNA was extracted with the PARIS™ Kit (#AM1921, Thermo Fisher) as previously reported [13]. RT-qPCR kits were purchased from TaKaRa Bio Inc (Dalian, China) and cDNA was synthesized according to the manufacturer's instruction.…”

Section: Quantitative Reverse-transcription Pcr (Rt-qpcr)mentioning

confidence: 99%

“…Recently, numerous circRNAs have found to be dysregulated in HCC. For example, CircBACH1 (hsa_circ_0061395) is signi cantly upregulated in HCC tissue and circBACH1 knockdown suppresses the proliferation and increased apoptosis of HCC cells by regulating p27 repression via HuR [13]. CircASAP1 acts as a ceRNA for miR-326 and miR-532-5p to mediates tumor-associated-macrophage (TAM) in ltration [14].…”

Section: Introductionmentioning

confidence: 99%

CircRNA circ-0110102 Function as Anti-oncogenic Gene in Hepatocellular Carcinoma through Modulating miR-580-5p/CCL2 Pathway

Wang¹,

Wei²,

Xu³

et al. 2020

Preprint

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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. 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, the interaction between hsa_circ_0110102 and miR-580-5p was predicted and verified by luciferase assay and RNA pull-down, indicating that hsa_circ_0110102 function as sponge of 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. These results concluded that 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. Conclusions These results indicating that hsa_circ_0110102 serves as a potential prognostic predictor or therapeutic target for HCC.

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“…Recently, numerous circRNAs have found to be dysregulated in HCC. For example, CircBACH1 (hsa_circ_0061395) is signi cantly upregulated in HCC tissue andcircBACH1 knockdown suppresses the proliferation and increased apoptosis of HCC cells by regulating p27 repression via HuR [8]. CircASAP1 acts as a ceRNA for miR-326 and miR-532-5p to mediates tumor-associated-macrophage (TAM) in ltration [9].…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Wei

et al. 2020

Preprint

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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.

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CircBACH1 (hsa_circ_0061395) promotes hepatocellular carcinoma growth by regulating p27 repression via HuR

Cited by 67 publications

References 47 publications

Circular RNA circDLC1 Inhibits MMP1-Mediated Liver Cancer Progression via Interaction with HuR

Circular RNA circDLC1 Inhibits MMP1-Mediated Liver Cancer Progression via Interaction with HuR

CircRNA circ-0110102 Function as Anti-oncogenic Gene in Hepatocellular Carcinoma through Modulating miR-580-5p/CCL2 Pathway

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

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