LncRNA XLOC_006390 promotes pancreatic carcinogenesis and glutamate metabolism by stabilizing c-Myc

He, Jun; Li, Fazhao; Zhou, Yan; Hou, Xuyang; Liu, Sushun; Li, Xinchun; Zhang, Yawei; Jing, Xiaoqian; Li, Yang

doi:10.1016/j.canlet.2019.11.021

Cited by 44 publications

(37 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The lncRNA-protein interaction plays an important role in the posttranslational modification of proteins via affecting the protein stability [25]. For instance, lncRNA-XLOC_006390 was reported to promote pancreatic carcinogenesis via blocking c-Myc ubiquitination and stabilizing c-Myc protein [26]. In the current study, the binding between LINC00476 and SETDB1 was confirmed using RNA pull-down and RIP assays.…”

Section: Discussionsupporting

confidence: 57%

LINC00476 suppresses the progression of non-small cell lung cancer via inducing the ubiquitination of SETDB1

Wang

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Long non-coding RNAs are involved in the tumorigenesis of non-small cell lung cancer (NSCLC). This study aims to investigate whether LINC00476 affects the proliferation, invasion, and migration of NSCLC cells via SETDB1-activated Wnt/β-catenin pathway. Method: The expression of LINC00476, SETDB1, Wnt1, and β-catenin were determined in NSCLC tumor tissues and the paired adjacent tissues, as well as in NSCLC cell lines and bronchial epithelioid cell lines. Cell proliferation, invasion, and migration were determined using cell counting kit-8 assay and Transwell assay. The relationship between LINC00476 and SETDB1 was elucidated using RNA pull-down, RNA immunoprecipitation, and ubiquitination assays. Result: LINC00476 was significantly downregulated, while SETDB1, Wnt1, and β-catenin were upregulated in NSCLC tumor tissues and cell lines compared to the normal ones. Overexpression of LINC00476 promoted the proliferation, invasion, and migration of NSCLC cells, as well as suppressed tumor growth in the mouse xenograft. Meanwhile, overexpression of LINC00476 induced the degradation of SETDB1 via promoting its ubiquitination. The simultaneous overexpression of LINC00476 and SETDB1 negated the inhibition of LINC00476 overexpression on the proliferation, invasion, and migration of NSCLC cells. Conclusion: LINC00476 acts as a tumor suppressor in NSCLC via downregulating SETDB1, which provides a novel target in treating NSCLC.

show abstract

Section: Discussionsupporting

confidence: 57%

LINC00476 suppresses the progression of non-small cell lung cancer via inducing the ubiquitination of SETDB1

Wang

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Phosphorylated ANXA2 interacts with MYC and inhibits ubiquitin-dependent proteasomal degradation of MYC protein in esophageal cancer [ 166 ]. LncRNA XLOC_006390, GLCC1 and LINC01638 also block ubiquitination of c-Myc [ 156 , 167 , 168 ]. What’s more, E3 ligase FBX28 mediated non-proteolytic ubiquitination of c-Myc can enhance c-Myc dependent transcription [ 169 ].…”

Section: Ubiquitination and Transcription Factorsmentioning

confidence: 99%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

220

164

View full text Add to dashboard Cite

Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic reprogramming is a highly complex process. Recent studies have observed that ubiquitination and deubiquitination are involved in the regulation of metabolic reprogramming in cancer cells. As one of the most important type of post-translational modifications, ubiquitination is a multistep enzymatic process, involved in diverse cellular biological activities. Dysregulation of ubiquitination and deubiquitination contributes to various disease, including cancer. Here, we discuss the role of ubiquitination and deubiquitination in the regulation of cancer metabolism, which is aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.

show abstract

“…Increasing numbers of lncRNA studies in PC have been reported 9 - 12 . However, detailed evidence elucidating the underlying functions of lncRNAs, especially their regulatory roles in driving the key proto-oncogenes and oncogenes in PC—such as Kras 11 , p53 12 and c-Myc 13 —remains scarce.…”

Section: Introductionmentioning

confidence: 99%

Methylation-mediated LINC00261 suppresses pancreatic cancer progression by epigenetically inhibiting c-Myc transcription

Liu¹,

Zheng²,

Zhang³

et al. 2020

Theranostics

View full text Add to dashboard Cite

Background: Due to the limitations of strategies for its early diagnosis and treatment, pancreatic cancer (PC) remains a substantial human health threat. We previously discovered a methylation-mediated lncRNA, LINC00261, which is downregulated in PC tissues. However, the underlying role of LINC00261 in PC remains largely unknown. Methods: Quantitative real-time PCR and in situ hybridization were performed to evaluate the expression levels of LINC00261 in PC, adjacent nontumor and normal pancreas tissues. The clinical significance of LINC00261 was assessed in multicenter PC samples. The functions of LINC00261 in PC were investigated by gain- and loss-of-function assays in vitro and in vivo . Potential downstream pathways and mechanisms were explored via RNA sequencing and bioinformatic analyses. RNA immunoprecipitation and chromatin immunoprecipitation assays were used to validate the underlying mechanisms. Pyrosequencing and targeted demethylation of the LINC00261 promoter were performed to explore the upstream epigenetic mechanisms and therapeutic potential. Results: LINC00261 was significantly downregulated in PC tissues, and its expression was positively associated with the prognosis of PC patients. Phenotypic studies indicated that LINC00261 overexpression significantly suppressed PC cell proliferation, migration and metastasis in vitro and in vivo . c-Myc was identified as a downstream target of LINC00261. LINC00261 repressed c-Myc transcription by physically interacting and binding with the bromo domain of p300/CBP, preventing the recruitment of p300/CBP to the promoter region of c-Myc and decreasing the H3K27Ac level. Moreover, the methylation level of the LINC00261 promoter was high in PC tissues and was correlated with poor prognosis. Targeted demethylation of the LINC00261 promoter inhibited PC progression both in vitro and in vivo . Conclusions: Our findings indicate that methylation-mediated LINC00261 suppresses PC progression by epigenetically repressing c-Myc expression. These findings expand the therapeutic potential of LINC00261, possibly providing evidence to support the development of epigenetic drugs or therapeutic strategies. This research adds further insights into the etiology of PC and indicates that LINC00261 may be a prognostic and therapeutic target in PC.

show abstract

LncRNA XLOC_006390 promotes pancreatic carcinogenesis and glutamate metabolism by stabilizing c-Myc

Cited by 44 publications

References 23 publications

LINC00476 suppresses the progression of non-small cell lung cancer via inducing the ubiquitination of SETDB1

LINC00476 suppresses the progression of non-small cell lung cancer via inducing the ubiquitination of SETDB1

The role of ubiquitination and deubiquitination in cancer metabolism

Methylation-mediated LINC00261 suppresses pancreatic cancer progression by epigenetically inhibiting c-Myc transcription

Contact Info

Product

Resources

About