A novel long non-coding RNA RP11-286H15.1 represses hepatocellular carcinoma progression by promoting ubiquitination of PABPC4

Jiang, Xiang; Wang, Ganggang; Liu, Yingyi; Mei, Chengjie; Yao, Ye; Wu, Xiaoling; Chen, Xi; Ma, Weijie; Li, Kun; Zhang, Zhonglin; Yuan, Yufeng

doi:10.1016/j.canlet.2020.11.038

Cited by 31 publications

(13 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, conventional HCC treatments, including surgical resection and transplantation, are only effective in patients diagnosed at early stages 3 . HCC is characterized with abnormal expression of a lot of genes 4 - 6 , which results in frequent occurrence and distant metastasis of tumor as well as poor prognosis of HCC patients 7 , 8 . So far, there is no particularly effective therapeutic options for advanced HCC patients 9 .…”

Section: Introductionmentioning

confidence: 99%

ENKUR expression induced by chemically synthesized cinobufotalin suppresses malignant activities of hepatocellular carcinoma by modulating β-catenin/c-Jun/MYH9/USP7/c-Myc axis

Hou¹,

Li²,

Luo³

et al. 2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

ENKUR plays a crucial role in lung and colorectal cancers. Chemically synthesized cinobufotalin (CB) showed its significant anti-cancer effect in nasopharyngeal carcinoma. However, the roles of ENKUR and CB along with their correlation are still unknown in hepatocellular carcinoma (HCC). In this study, ENKUR expression in HCC tissue and cells were detected. The relationship between ENKUR expression and clinical pathology was also assessed. In vivo and in vitro experiments were conducted to explore the effects and molecular basis of ENKUR and CB in HCC. ENKUR expression was correlated with HCC progression and patient prognosis. Furthermore, ENKUR could inhibit tumor proliferation, metastasis, and sorafenib resistance in HCC. Mechanistic studies showed that ENKUR or its Enkurin domain could bind to MYH9 and decrease its expression by binding to β-catenin and inhibiting its nuclear transfer, thus decreasing c-Jun level. Low expression of MYH9 suppressed recruitment of deubiquitination enzyme USP7, promoting degradation of the c-Myc. Therefore, cell cycle and EMT signals were suppressed. CB as a safe and effective anti-cancer compound up-regulates the expression of ENKUR via inhibiting PI3K/AKT/c-Jun-mediated transcription suppression. These findings show that ENKUR induced by CB antagonizes β-catenin/c-Jun/MYH9/USP7 pathway, thus increasing c-Myc ubiquitin degradation and finally suppressing cell cycle and EMT signals.

show abstract

Section: Introductionmentioning

confidence: 99%

ENKUR expression induced by chemically synthesized cinobufotalin suppresses malignant activities of hepatocellular carcinoma by modulating β-catenin/c-Jun/MYH9/USP7/c-Myc axis

Hou¹,

Li²,

Luo³

et al. 2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

show abstract

“…Hepatocellular carcinoma (HCC) is one of the most common malignant tumours with the characteristics of invasion and metastasis, and has high morbidity and mortality worldwide 1,2 . At present, comprehensive treatments such as surgical resection, liver transplantation, radiofrequency ablation and transarterial chemoembolization are the main treatment options for HCC and are only effective for patients with early diagnosis 3,4 . However, some patients with HCC experienced early recurrence after surgery.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 At present, comprehensive treatments such as surgical resection, liver transplantation, radiofrequency ablation and transarterial chemoembolization are the main treatment options for HCC and are only effective for patients with early diagnosis. 3,4 However, some patients with HCC experienced early recurrence after surgery.Ethics approval and consent to participate: The studies involving human participants were reviewed and approved by the…”

mentioning

confidence: 99%

DNASE1L3 inhibits proliferation, invasion and metastasis of hepatocellular carcinoma by interacting with β‐catenin to promote its ubiquitin degradation pathway

Yan

et al. 2022

Cell Proliferation

View full text Add to dashboard Cite

As a member of the deoxyribonuclease 1 family, DNASE1L3 plays a significant role both inside and outside the cell. However, the role of DNASE1L3 in hepatocellular carcinoma (HCC) and its molecular basis remains to be further investigated. In this study, we report that DNASE1L3 is downregulated in clinical HCC samples and evaluate the relationship between its expression and HCC clinical features. In vivo and in vitro experiments showed that DNASE1L3 negatively regulates the proliferation, invasion and metastasis of HCC cells. Mechanistic studies showed that DNASE1L3 recruits components of the cytoplasmic β‐catenin destruction complex (GSK‐3β and Axin), promotes the ubiquitination degradation of β‐catenin, and inhibits its nuclear transfer, thus, decreasing c‐Myc, P21 and P27 level. Ultimately, cell cycle and EMT signals are restrained. In general, this study provides new insight into the mechanism for HCC and suggests that DNASE1L3 can become a considerable target for HCC.

show abstract

“…In colorectal cancer, SNHG17 lncRNA inhibited PES1 ubiquitination and degradation via blocking the interaction of Trim23 and PES1 [ 35 ]. Jiang et al reported that RP11-286H15.1 lncRNA bound to PABPC4 via 620–750 nucleotides of RP11-286H15.1 and ubiquitinated PABPC4 via TRIM37 in hepatocellular carcinoma [ 36 ]. Therefore, lncRNAs located in the cytoplasm probably interact with ubiquitinase enzymes to regulate the stability and expression of the target protein, thus exerting a tumor-promoting or tumor-suppressing role.…”

Section: Discussionmentioning

confidence: 99%

LINC00941 promotes pancreatic cancer malignancy by interacting with ANXA2 and suppressing NEDD4L-mediated degradation of ANXA2

Wang

Liu

et al. 2022

Cell Death Dis

View full text Add to dashboard Cite

Recently, long non-coding RNAs (lncRNA) have been proven to regulate pancreatic cancer (PC) progression. We aimed to explore the pathogenesis of LINC00941 in PC regarding protein binding. By using PCR analysis, we found that LINC00941 was overexpressed in PC tissues and was higher in patients with liver metastasis than in patients without liver metastasis. In addition, high LINC00941 expression was associated with a poor prognosis. Functional experiments and mice models were respectively used to evaluate PC cell proliferation and migration in vitro and in vivo. The results suggested that LINC00941 overexpression promoted PC proliferation and metastasis. Subsequently, RNA pull-down, mass spectrometry (MS), and RNA-binding protein immunoprecipitation (RIP) were performed to identify LINC00941-interacting proteins. The results suggested that ANXA2 was the potential LINC00941-interacting protein. Nucleotides 500–1390 of LINC00941 could bind to the Annexin 1 domain of ANXA2. LINC00941-mediated malignant phenotype of PC was reversed by ANXA2 depletion. Co-immunoprecipitation (Co-IP) followed by MS was conducted to determine the potential interacting protein of LINC00941. The results illustrated that NEDD4L, an E3 ligase involved in ubiquitin-mediated protein degradation, bound to the Annexin 1 domain of ANXA2 and promoted its degradation. Mechanically, LINC00941 functioned as a decoy to bind to ANXA2 and suppressed its degradation by enclosing the domain that binds to NEDD4L. Eventually, LINC00941 upregulated ANXA2 and activated FAK/AKT signaling, increasing PC cell proliferation and metastasis. This study indicates that LINC00941 promotes PC proliferation and metastasis by binding ANXA2 and potentiating its stability, leading to the activation of FAK/AKT signaling. Our data demonstrate that LINC00941 may serve as a novel target for prognosis and therapy.

show abstract

A novel long non-coding RNA RP11-286H15.1 represses hepatocellular carcinoma progression by promoting ubiquitination of PABPC4

Cited by 31 publications

References 38 publications

ENKUR expression induced by chemically synthesized cinobufotalin suppresses malignant activities of hepatocellular carcinoma by modulating β-catenin/c-Jun/MYH9/USP7/c-Myc axis

ENKUR expression induced by chemically synthesized cinobufotalin suppresses malignant activities of hepatocellular carcinoma by modulating β-catenin/c-Jun/MYH9/USP7/c-Myc axis

DNASE1L3 inhibits proliferation, invasion and metastasis of hepatocellular carcinoma by interacting with β‐catenin to promote its ubiquitin degradation pathway

LINC00941 promotes pancreatic cancer malignancy by interacting with ANXA2 and suppressing NEDD4L-mediated degradation of ANXA2

Contact Info

Product

Resources

About