Circ_0036412 affects the proliferation and cell cycle of hepatocellular carcinoma via hedgehog signaling pathway

Wang, Liyan; Li, Bin; Yi, Xiaoyuan; Xiao, Xuejun; Zheng, Qianqian; Ma, Lei

doi:10.1186/s12967-022-03305-x

Cited by 18 publications

(14 citation statements)

References 44 publications

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“…It’s reported that circZNF609 sequestering microRNA-150 plays a role in promoting colorectal cancer progression by upregulating Gli1 expression [ 88 ]. Moreover, several circRNAs such as circSMO742 [ 89 ], circ-STAT3 [ 90 ], circ_0036412 [ 91 ] and circDCAF6 [ 92 ] could act as miRNA sponges to affect some cancer hallmarks.…”

Section: Introductionmentioning

confidence: 99%

Noncoding RNAs related to the hedgehog pathway in cancer: clinical implications and future perspectives

Song

Sun

et al. 2022

Mol Cancer

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Cancer is a type of malignant affliction threatening human health worldwide; however, the molecular mechanism of cancer pathogenesis remains to be elusive. The oncogenic hedgehog (Hh) pathway is a highly evolutionarily conserved signaling pathway in which the hedgehog-Patched complex is internalized to cellular lysosomes for degradation, resulting in the release of Smoothened inhibition and producing downstream intracellular signals. Noncoding RNAs (ncRNAs) with diversified regulatory functions have the potency of controlling cellular processes. Compelling evidence reveals that Hh pathway, ncRNAs, or their crosstalk play complicated roles in the initiation, metastasis, apoptosis and drug resistance of cancer, allowing ncRNAs related to the Hh pathway to serve as clinical biomarkers for targeted cancer therapy. In this review, we attempt to depict the multiple patterns of ncRNAs in the progression of malignant tumors via interactions with the Hh crucial elements in order to better understand the complex regulatory mechanism, and focus on Hh associated ncRNA therapeutics aimed at boosting their application in the clinical setting.

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Section: Introductionmentioning

confidence: 99%

Noncoding RNAs related to the hedgehog pathway in cancer: clinical implications and future perspectives

Song

Sun

et al. 2022

Mol Cancer

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“…42 Here, we demonstrated that circSLC39A5 was also down- Increasing evidence shows that circRNAs can play a key role in HCC proliferation, such as regulating stem cell characteristics, 43 affecting the expression of Ki67 and AFP, 44 and controlling tumor cell cycle arrest and cell senescence. [45][46][47] circRNAs can also affect the apoptosis of cancer cells and thus affect the programmed cell death of HCC, 48,49 or influence HCC invasion and metastasis by affecting the epithelial-to-mesenchymal transition (EMT). 50,51 Here, in vitro and in vivo experiments manifested that circSLC39A5 inhibited the proliferation, migration, and invasion of HCC cells, promoted cells apoptosis, and was associated with low expression of proliferation index Ki67 and capillarity marker CD34.…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidence shows that circRNAs can play a key role in HCC proliferation, such as regulating stem cell characteristics, 43 affecting the expression of Ki67 and AFP, 44 and controlling tumor cell cycle arrest and cell senescence 45–47 . circRNAs can also affect the apoptosis of cancer cells and thus affect the programmed cell death of HCC, 48,49 or influence HCC invasion and metastasis by affecting the epithelial‐to‐mesenchymal transition (EMT) 50,51 .…”

Section: Discussionmentioning

confidence: 99%

Nucleus‐localized circSLC39A5 suppresses hepatocellular carcinoma development by binding to STAT1 to regulate TDG transcription

Liu,

Lai,

et al. 2023

Cancer Science

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Accumulating evidence indicates that circular RNAs (circRNAs) are inextricably linked to cancer development. However, the function and mechanism of nucleus‐localized circRNAs in hepatocellular carcinoma (HCC) still require investigation. Here, qRT‐PCR and receiver‐operating characteristic curve were used to detect the expression and diagnostic potential of circSLC39A5 for HCC. The biological function of circSLC39A5 in HCC was investigated in vitro and in vivo. Nucleoplasmic separation assay, fluorescence in situ hybridization, RNA pulldown, RNA immunoprecipitation, the HDOCK Server, the NucleicNet Webserver, crosslinking‐immunoprecipitation, MG132 treatment, and chromatin immunoprecipitation were utilized to explore the potential molecular mechanism of circSLC39A5 in HCC. The results showed that circSLC39A5 was downregulated in both HCC tissues and plasma and was associated with satellite nodules and lymph node metastasis/vascular invasion. CircSLC39A5 was stably expressed in plasma samples under different storage conditions, showing good diagnostic potential for HCC (AUC = 0.915). CircSLC39A5 inhibited proliferation, migration, and invasion, facilitated the apoptosis of HCC cells, and was associated with low expression of Ki67 and CD34. Remarkably, circSLC39A5 is mainly localized in the nucleus and binds to the transcription factor signal transducer and activator of transcription 1 (STAT1), affecting its stabilization and expression. STAT1 binds to the promoter of thymine DNA glycosylase (TDG). Overexpression of circSLC39A5 elevates TDG expression and reverses the increase of proliferating cell nuclear antigen (PCNA) expression and the overactive cell proliferation caused by TDG silencing. Our findings uncovered a novel plasma circRNA, circSLC39A5, which may be a potential circulating diagnostic marker for HCC, and the mechanism by which nucleus‐localized circSLC39A5 exerts a transcriptional regulatory role in HCC by affecting STAT1/TDG/PCNA provides new insights into the mechanism of circRNAs.

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“…An increasing number of experiments have demonstrated that circRNAs can promote the development of HCC by regulating various signals involved with the cell cycle, proliferation, differentiation, cell survival and apoptosis, leading to abnormal activation of several molecules in signal transduction pathways [18] . Studies have con rmed that circRNAs can act via the AKT/ERK [19] , Wnt/βcatenin [20] , nuclear factor-kappa B [21], hedgehog [22] , c-Met [23] , JAK2/STAT3 [24] and other signalling pathways and are involved in the malignant biological behaviours of HCC. Recent studies have con rmed that circRNAs not only exert biological functions through the above signalling pathways but also affect the biological processes of HCC through other pathways.…”

Section: Discussionmentioning

confidence: 99%

RNA-sep analysis of circular RNAs and ceRNA networks in human hepatocellular carcinoma

Liu

Dong

Chen

et al. 2022

Preprint

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Objective An increasing number of circular RNAs (circRNAs) have been identified as emerging competing endogenous RNAs (ceRNAs) that play important roles in hepatocellular carcinoma (HCC), but numerous circRNAs remain unexplored. The aim of this study was to explore the mechanism of action of differentially expressed circRNAs and their ceRNA networks in HCC. Methods Second-generation sequencing technology was used to analyse the expression of circRNAs in cancerous and paired paraneoplastic tissues from five patients with HCC. The circRNAs with a P value of less than 0.01, with an original signal value greater than 100 and ranked among the top ten upregulated circRNAs were selected and validated by quantitative reverse transcription polymerase chain reaction (qRT‒PCR) in paired cancer and paraneoplastic tissues from another 34 HCC patients. The downstream miRNAs and mRNAs of the circRNAs were explored through database analysis, and finally, the ceRNA networks and circRNA–miRNA–mRNA axes based on these ten circRNAs were constructed. Results By sequencing, we identified 9658 differentially expressed circRNAs on all chromosomes, of which 3862 were significantly upregulated and 5796 were significantly downregulated. RT-qPCR was performed to validate the top ten upregulated circRNAs, and the results were generally consistent with the sequencing results. After qRT‒PCR validation, five circRNAs (hsa_circ_0079875, hsa_circ0091580, hsa_circ0091581, hsa_circ0004788 and hsa_circ_0059730) were selected for further analysis. First, the downstream miRNAs and mRNAs of these five circRNAs were predicted to construct circRNA-miRNA‒mRNA network diagrams. The 1482 upregulated mRNAs identified in the GEPIA database overlapped with the 278 mRNAs in the ceRNA networks, and 14 overlapping genes were identified. Further bioinformatics analysis revealed four mRNAs (ADSL, AP3B1, MAPRE1, and TRNP1) and five circRNA–miRNA–mRNA axes that were negatively correlated with HCC prognosis. Conclusions Numerous differentially expressed circRNAs exist in HCC, and most can regulate the biological behaviour of HCC through circRNA-miRNA‒mRNA networks. Bioinformatics analysis showed that the ceRNA regulatory axes in HCC have high diagnostic and prognostic value and deserve further exploration. This study aims to provide new research ideas related to HCC pathogenesis and treatment options.

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Circ_0036412 affects the proliferation and cell cycle of hepatocellular carcinoma via hedgehog signaling pathway

Cited by 18 publications

References 44 publications

Noncoding RNAs related to the hedgehog pathway in cancer: clinical implications and future perspectives

Noncoding RNAs related to the hedgehog pathway in cancer: clinical implications and future perspectives

Nucleus‐localized circSLC39A5 suppresses hepatocellular carcinoma development by binding to STAT1 to regulate TDG transcription

RNA-sep analysis of circular RNAs and ceRNA networks in human hepatocellular carcinoma

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