A novel lncRNA uc.134 represses hepatocellular carcinoma progression by inhibiting CUL4A-mediated ubiquitination of LATS1

Ni, Weijian; Zhang, Yuqin; Zhan, Zongxiang; Feng, Yang; Liang, Yonghao; Huang, Jing; Chen, Keli; Chen, Longhua; Ding, Yi

doi:10.1186/s13045-017-0449-4

Cited by 189 publications

(151 citation statements)

References 54 publications

(57 reference statements)

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“…HCC is a leading cause of cancer-associated mortality worldwide, and tumor recurrence and metastasis are major factors that contribute to the poor prognosis of HCC patients (29,30). Previous studies have confirmed that protein ubiquitination serves multiple roles in different biological processes.…”

Section: Discussionmentioning

confidence: 99%

High expression of ubiquitin-conjugating enzyme E2A predicts poor prognosis in hepatocellular carcinoma

Shen

et al. 2018

Oncol Lett

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Abstract. The present study aimed to illustrate the association of the expression of ubiquitin-conjugating enzyme E2A (UBE2A) with the clinicopathological parameters and prognosis in hepatocellular carcinoma (HCC). The expression levels of UBE2A mRNA and protein in a total of 276 HCC tissues and six liver cell lines was detected by fluorescent quantitative polymerase chain reaction, western blotting and immunohistochemistry. Statistical analysis was also performed to assess the association of the expression of UBE2A with the clinicopathological parameters and prognosis by the GraphPad Prism and SPSS version 21.0 software. UBE2A mRNA and protein were highly expressed in HCC tissues compared with those in the adjacent normal tissue. Immunohistochemical analysis revealed that UBE2A protein was more strongly stained in the 276 paraffin-embedded HCC tissues as compared with the 63 adjacent normal tissue. Statistical analysis also demonstrated that UBE2A expression was significantly associated with histological differentiation, TNM stage and vascular invasion of HCC (P<0.05). Notably, HCC patients with a high expression of UBE2A had a shorter survival time as compared with those with a low expression of UBE2A. There results suggested that UBE2A may be involved in the pathogenesis of HCC and may serve as an important prognostic marker.Further exploration of the involvement of UBE2A in HCC development may provide novel therapeutic targets. IntroductionHepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide and the fifth most common cancer type (1). HCC is a global health burden and its prevalence varies worldwide (2). The incidence rate is reported to be higher in Asia (>20 cases/100,000 individuals) in comparison with that in North America and Europe (<5 cases/100,000 individuals) (3). The prognosis of HCC is poor, as evident by the fact that the number of annual mortality cases (~600,000) is almost equal to the number of new cases diagnosed annually (4). The median rate for 1-year survival is 80% (range, 63-97%), for 3-year survival is 70% (range, 34-78%) and for 5-year survival is 50% (range, 17-69%) (5). Surgery remains the most important treatment strategy for patients with HCC. The 5-year survival rate of patients with early HCC subsequent to resection treatment reaches 50%, although these patients exhibit a high recurrence rate (6,7). Despite advances in the diagnosis (8) and treatment (9) of HCC, the prognosis of this disease remains poor (10). Therefore, further clarification of the mechanisms underlying its development is important (11,12).At present, the prognosis of HCC is predicted based on imaging findings and biomarkers. Various biomarkers, including α-fetoprotein (AFP) (13), des-γ-ca rboxy prothrombin (14) and α-l-fucosidase (15), have been identified over the past three decades. However, accurate indicators for the prognosis of HCC are limited. Consequently, there is an urgency to develop a novel biomarker for the prognosis of HCC.The ubiquitin system serves a ...

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Section: Discussionmentioning

confidence: 99%

High expression of ubiquitin-conjugating enzyme E2A predicts poor prognosis in hepatocellular carcinoma

Shen

et al. 2018

Oncol Lett

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“…For example, lnc-EGFR accelerates T-regulatory cell differentiation leading to immune evasion of HCC [6], and a variety of lncRNAs, such as MALT1 [7], TP73-AS1 [8], HULC [9], XIST [10], and HOTAIR [11], function as oncogenes, promoting HCC growth and metastasis by regulating miRNA or proteins. However, lncRNA uc.134 and lincRNA-p21 inhibit HCC progression by repressing CUL4A-mediated ubiquitination of LATS1 [12] or activating endoplasmic reticulum stress [13]. These findings indicate lncRNAs are potential prognostic factors for HCC.…”

Section: Introductionmentioning

confidence: 93%

lncRNA SNHG8 Promotes the Tumorigenesis and Metastasis by Sponging miR-149-5p and Predicts Tumor Recurrence in Hepatocellular Carcinoma

Dong

Teng

Guo

et al. 2018

Cell Physiol Biochem

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Background/Aims: Long noncoding RNAs (lncRNAs) are aberrantly expressed in multiple malignant tumors involved in tumor growth and metastasis. Accumulating data show that small nucleolar RNA host gene (SNHG) 1/12/20 plays a key role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms by which SNHG8 contributes to HCC remain elusive and merit exploration. Methods: The association between SNHG8 expression and the clinicopathological characteristics and prognoses in HCC patients was analysed by using qRT-PCR analysis and the data from The Cancer Genome Atlas. Cell growth and metastatic potential were determined by MTT, colony formation, Transwell assays, and the mouse xenograft tumor model and lung metastasis model. Epithelial–mesenchymal transition markers were detected by western blot analysis. The binding capacity of SNHG8 with miRNAs was evidenced by bioinformatic analysis and a luciferase reporter assay. In addition, the rescue experiments were performed based on co-transfection with sh-SNHG8 and a miR-149 inhibitor in HCC cells. Results: The expression levels of lncRNA SNHG8 were dramatically increased in HCC tissues and cell lines as compared with the adjacent normal tissues, and SNHG8 expression was an independent prognostic factor of tumor recurrence in HCC patients. Furthermore, knockdown of SNHG8 inhibited cell proliferation, invasion, and lung metastasis in vitro and in vivo, whereas overexpression of SNHG8 reversed these effects. SNHG8 acted as a sponge of miR-149 and counteracted the tumor suppressive effects of mi R-149 in HCC cells. Expression of phosphatase, Mg2+/Mn2+ dependent 1F, a target of R-149, displayed a negative correlation with miR-149 expression but a positive correlation with SNHG8 expression in HCC specimens. Conclusion: As lncRNA SNHG8 may promote HCC tumorigenesis and metastasis by sponging miR-149, it is a potential candidate marker and therapeutic target for HCC.

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“…It has been widely recognized that many lncRNAs are dysregulated and play an important part in cancer progression [2]. In HCC, lncRNAs have been reported to affect various malignant phenotypes, such as cell proliferation, motility, and glucose metabolism reprogramming [3][4][5]. However, investigations of the involvement of lncRNAs in aberrant lipid metabolism in HCC are few.…”

Section: Introductionmentioning

confidence: 99%

M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

et al. 2020

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Background: Long non-coding RNAs (lncRNAs) possess significant regulatory functions in multiple biological and pathological processes, especially in cancer. Dysregulated lncRNAs in hepatocellular carcinoma (HCC) and their therapeutic applications remain unclear.Methods: Differentially expressed lncRNA profile in HCC was constructed using TCGA data. LINC00958 expression level was examined in HCC cell lines and tissues. Univariate and multivariate analyses were performed to demonstrate the prognostic value of LINC00958. Loss-of-function and gain-of-function experiments were used to assess the effects of LINC00958 on cell proliferation, motility, and lipogenesis. Patient-derived xenograft model was established for in vivo experiments. RNA immunoprecipitation, dual luciferase reporter, biotin-labeled miRNA pulldown, fluorescence in situ hybridization, and RNA sequencing assays were performed to elucidate the underlying molecular mechanisms. We developed a PLGA-based nanoplatform encapsulating LINC00958 siRNA and evaluated its superiority for systemic administration. Results:We identified a lipogenesis-related lncRNA, LINC00958, whose expression was upregulated in HCC cell lines and tissues. High LINC00958 level independently predicted poor overall survival. Functional assays showed that LINC00958 aggravated HCC malignant phenotypes in vitro and in vivo. Mechanistically, LINC00958 sponged miR-3619-5p to upregulate hepatoma-derived growth factor (HDGF) expression, thereby facilitating HCC lipogenesis and progression. METTL3-mediated N 6 -methyladenosine modification led to LINC00958 upregulation through stabilizing its RNA transcript. A PLGA-based nanoplatform loaded with si-LINC00958 was developed for HCC systemic administration. This novel drug delivery system was controlled release, tumor targeting, safe, and presented satisfactory antitumor efficacy.

show abstract

A novel lncRNA uc.134 represses hepatocellular carcinoma progression by inhibiting CUL4A-mediated ubiquitination of LATS1

Cited by 189 publications

References 54 publications

High expression of ubiquitin-conjugating enzyme E2A predicts poor prognosis in hepatocellular carcinoma

High expression of ubiquitin-conjugating enzyme E2A predicts poor prognosis in hepatocellular carcinoma

lncRNA SNHG8 Promotes the Tumorigenesis and Metastasis by Sponging miR-149-5p and Predicts Tumor Recurrence in Hepatocellular Carcinoma

M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

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