Circular RNA hsa_circ_0062682 Binds to YBX1 and Promotes Oncogenesis in Hepatocellular Carcinoma

Razpotnik, Rok; Vidmar, Robert; Fonović, Marko; Rozman, Damjana; Režen, Tadeja

doi:10.3390/cancers14184524

Cited by 9 publications

(7 citation statements)

References 99 publications

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“…[16] As a multifaceted molecule, YBX1 functions as a transcription factor when located in the nucleus, [17] whereas it typically serves as an RNA-binding protein in the cytoplasm. [10] Numerous studies have reported that YBX1 promotes tumor growth and metastasis in various cancer types including HCC, [8,18] colorectal cancer, [9] and clear cell renal cell carcinoma. [11] Notably, Chen et al demonstrated a novel role of YBX1 in stabilizing the heparin-binding growth factor (HDGF) mRNA by targeting the m5C-modified site in bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

“…It modulates the stability of target transcripts by recognizing the m5C modification. [ 7a ] Previous studies have demonstrated the oncogenic function of YBX1 as an RNA‐binding protein in tumorigenesis and cancer metastasis such as hepatocellular carcinoma (HCC), [ 8 ] colorectal cancer, [ 9 ] Chronic myeloid leukemia [ 10 ] and clear cell renal cell carcinoma. [ 11 ] Recently, increasing evidence has demonstrated that YBX1 functions as an m5C reader in bladder, [ 7a ] breast, [ 12 ] and gynecologic cancers.…”

Section: Introductionmentioning

confidence: 99%

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YBX1 Promotes Esophageal Squamous Cell Carcinoma Progression via m5C‐Dependent SMOX mRNA Stabilization

Liu,

Chen,

Zhang

et al. 2024

Advanced Science

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The modification and recognition of 5‐methylcytosine (m5C) are involved in the initiation and progression of various tumor types. However, the precise role and potential mechanism of Y‐box‐binding protein 1 (YBX1) in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, it is found that YBX1 is frequently upregulated in ESCC compared with matched nontumor tissues. Gain‐ and loss‐of‐function assays show that YBX1 promoted the proliferation and metastasis of ESCC cells both in vitro and in vivo. Functional studies revealed that NOP2/Sun RNA methyltransferase family member 2 (NSUN2) is a critical RNA methyltransferase that facilitates YBX1‐mediated ESCC progression. Mechanistically, integrated analysis based on RNA immunoprecipitation sequencing (RIP‐seq) and m5C methylated RNA immunoprecipitation and sequencing (MeRIP‐seq) assays identified spermine oxidase (SMOX) as a target gene containing an m5C site in its coding sequence (CDS) region, which coincided well with the binding site of YBX1. Overexpression of SMOX‐WT but not SMOX‐Mut partially restored the proliferation and invasion ability of ESCC cells curbed by YBX1 knockdown. Moreover, YBX1 activated the mTORC1 signaling pathway by stabilizing SMOX mRNA. The study reveals that YBX1 promotes ESCC development by stabilizing SMOX mRNA in an m5C‐dependent manner, thus providing a valuable therapeutic target for ESCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

YBX1 Promotes Esophageal Squamous Cell Carcinoma Progression via m5C‐Dependent SMOX mRNA Stabilization

Liu,

Chen,

Zhang

et al. 2024

Advanced Science

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“…Razpotnik et al identified an upregulated circRNA, hsa_circ_0062682, that could interact with YBX1 in hepatocellular carcinoma. Knockdown of hsa_circ_0062682 revealed the transcription factors E2F1, Sp1, HIF-1α, and NFκB1 as potential downstream targets [ 44 ]. However, this study did not explore the relationship between YBX1 and E2F1.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0007990 promotes breast cancer growth via inhibiting YBX1 protein degradation to activate E2F1 transcription

Xu,

Xiong,

Hong

et al. 2024

Cell Death Dis

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Breast cancer (BC) is the most commonly diagnosed malignant tumour in females worldwide. Although remarkable advances in early detection and treatment strategies have led to decreased mortality, recurrence and metastasis remain the major causes of cancer death in BC patients. Increasing evidence has demonstrated that circular RNAs (circRNAs) play critical roles in cancer progression. However, the detailed biological functions and molecular mechanisms of circRNAs in BC are unclear. The aim of this study was to investigate the possible role of circRNAs in the progression of BC. Differentially expressed circRNAs in BC were identified by integrating breast tumour-associated somatic CNV data and circRNA high-throughput sequencing. Aberrant hsa_circ_0007990 expression and host gene copy number were detected in BC cell lines via quantitative polymerase chain reaction (qPCR). The expression level of hsa_circ_0007990 in BC tissues was validated by in situ hybridization (ISH). Loss- and gain-of-function experiments were performed in vitro and in vivo, respectively, to explore the potential biological function of hsa_circ_0007990 in BC. The underlying mechanisms of hsa_circ_0007990 were investigated through MS2 RNA pull-down, RNA immunoprecipitation, RNA fluorescence in situ hybridization, immunofluorescence, chromatin immunoprecipitation and luciferase reporter assays. The levels of hsa_circ_0007990 were elevated in BC tissues and cell lines, an effect that was partly due to host gene copy number gains. Functional assays showed that hsa_circ_0007990 promoted BC cell growth. Mechanistically, hsa_circ_0007990 could bind to YBX1 and inhibit its degradation by preventing ubiquitin/proteasome-dependent degradation, thus enhancing the expression of the cell cycle-associated gene E2F1. Rescue experiments suggested that hsa_circ_0007990 promoted BC progression through YBX1. In general, our study demonstrated that hsa_circ_0007990 modulates the ubiquitination and degradation of YBX1 protein and further regulates E2F1 expression to promote BC progression. We explored the possible function and molecular mechanism of hsa_circ_0007990 in BC and identified a novel candidate target for the treatment of BC.

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“…The YBX1 protein was identified to bind with circ_0062682. However, the precise downstream molecular mechanisms of this circ_0062682 and YBX1 interplay on HCC progression remain a subject warranting further exploration [ 130 ].…”

Section: Ncrnas Regulate Methylation-related Proteins In Hccmentioning

confidence: 99%

Non-coding RNA methylation modifications in hepatocellular carcinoma: interactions and potential implications

Shi,

Chu,

Zeng

et al. 2023

Cell Commun Signal

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RNA methylation modification plays a crucial role as an epigenetic regulator in the oncogenesis of hepatocellular carcinoma (HCC). Numerous studies have investigated the molecular mechanisms underlying the methylation of protein-coding RNAs in the progression of HCC. Beyond their impact on mRNA, methylation modifications also influence the biological functions of non-coding RNAs (ncRNAs). Here, we present an advanced and comprehensive overview of the interplay between methylation modifications and ncRNAs in HCC, with a specific focus on their potential implications for the tumor immune microenvironment. Moreover, we summarize promising therapeutic targets for HCC based on methylation-related proteins. In the future, a more profound investigation is warranted to elucidate the effects of ncRNA methylation modifications on HCC pathogenesis and devise valuable intervention strategies.

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Circular RNA hsa_circ_0062682 Binds to YBX1 and Promotes Oncogenesis in Hepatocellular Carcinoma

Cited by 9 publications

References 99 publications

YBX1 Promotes Esophageal Squamous Cell Carcinoma Progression via m5C‐Dependent SMOX mRNA Stabilization

YBX1 Promotes Esophageal Squamous Cell Carcinoma Progression via m5C‐Dependent SMOX mRNA Stabilization

Hsa_circ_0007990 promotes breast cancer growth via inhibiting YBX1 protein degradation to activate E2F1 transcription

Non-coding RNA methylation modifications in hepatocellular carcinoma: interactions and potential implications

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