LINC00680 enhances hepatocellular carcinoma stemness behavior and chemoresistance by sponging miR-568 to upregulate AKT3

Shu, Gege; Su, Huizhao; Wang, Zhiqian; Lai, Shihui; Wang, Yan; Liu, Xiaomeng; Dai, Luo; Bi, Yin; Chen, Wei; Huang, Weiguo; Zhou, Ziyan; He, Songqing; Dai, Huanyun; Tang, Bo

doi:10.1186/s13046-021-01854-5

Cited by 33 publications

(20 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…found that PVT1 promotes gemcitabine resistance in pancreatic cancer by activating the Wnt/β-catenin and autophagy pathways by modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes ( 12 ). In addition, LINC00680 promotes hepatocellular carcinoma stemness properties and decreases chemosensitivity by sponging miR-568 to activate AKT3 expression ( 13 ). Our previous studies and others also revealed that lncRNAs play critical roles in the chemoresistance of PCa, including HOTAIR, NEAT1, DANCR, MALAT1 and CASC2 ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

TFAP2C-Mediated lncRNA PCAT1 Inhibits Ferroptosis in Docetaxel-Resistant Prostate Cancer Through c-Myc/miR-25-3p/SLC7A11 Signaling

Jiang

Guo

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

Recent evidence has shown that the induction of ferroptosis is a new therapeutic strategy for advanced prostate cancer (PCa) when used as a monotherapy or in combination with second-generation antiandrogens. However, whether ferroptosis inducers are effective against docetaxel-resistant PCa remains unclear. In addition, the biological role and intrinsic regulatory mechanisms of long noncoding RNAs (lncRNAs) in ferroptosis and chemoresistance are not well understood. In this study, we established two acquired docetaxel-resistant PCa cell lines and found that docetaxel-resistant PCa cells developed tolerance toward ferroptosis. In addition, dysregulated lncRNAs in drug-resistant and -sensitive PCa cells were identified by RNA sequencing, and we identified that prostate cancer-associated transcript 1 (PCAT1) was highly expressed in the docetaxel-resistant PCa cell lines and clinical samples. Overexpression of PCAT1 inhibited ferroptosis and increased docetaxel resistance, which could be attenuated by PCAT1 knockdown. Furthermore, we revealed that PCAT1 inhibited ferroptosis by activating solute carrier family 7-member 11 (SLC7A11) expression via reducing iron accumulation and subsequent oxidative damage. Mechanistically, we demonstrated that PCAT1 interacted with c-Myc and increased its protein stability using nucleotides 1093-1367 of PCAT1 and 151-202 amino acids of c-Myc protein, thereby transcriptionally promoting SLC7A11 expression. In addition, PCAT1 facilitated SLC7A11 expression by competing for microRNA-25-3p. Finally, transcription factor AP-2 gamma (TFAP2C) activated PCAT1 expression at the transcriptional level to reduce ferroptosis susceptibility and enhance chemoresistance. Collectively, our findings demonstrated that TFAP2C-induced PCAT1 promotes chemoresistance by blocking ferroptotic cell death through c-Myc/miR-25-3p/SLC7A11 signaling.

show abstract

Section: Introductionmentioning

confidence: 99%

TFAP2C-Mediated lncRNA PCAT1 Inhibits Ferroptosis in Docetaxel-Resistant Prostate Cancer Through c-Myc/miR-25-3p/SLC7A11 Signaling

Jiang

Guo

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Results from cell proliferation assay revealed that knockdown of LINC00680 had the most dramatic effects on cell proliferation. Previous studies have demonstrated the oncogenic role of LINC00680 in lung cancer [ 21 , 22 ], hepatocellular carcinoma [ 23 ] and glioblastoma [ 24 ], but the functions, molecular mechanisms, and clinical relevance of LINC00680 in ESCC remains largely unknown. In the present study, we demonstrated that LINC00680 acts as an oncogenic lncRNA, which is significantly enriched in ESCC tumor tissues compared to the adjacent normal epithelial tissues, related with tumor size, depth of invasion, lymph node metastasis, and TNM stage, and predicted worse clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…We concluded that LINC00680 regulates PAK6 expression by competitively binding to miR-423-5p, and accelerates tumorigenesis of ESCC cells. It should also be noted that LINC00680 can also sponge miR-568 to upregulate the expression of AKT3 in hepatocellular carcinoma to enhance carcinogenetic stemness behavior and chemoresistance [ 23 ]. Therefore, the potential of LINC00680 as a prognostic biomarker and therapeutic target in lncRNA-based cancer therapy warrants further exploration.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis

et al. 2022

View full text Add to dashboard Cite

Background Esophageal squamous cell carcinoma (ESCC) is a common invasive malignancy worldwide with poor clinical outcomes. Increasing amount of long non-coding RNAs (lncRNAs) have been reported to be involved in cancer development. However, lncRNAs that are functional in ESCC and the underlying molecular mechanisms remain largely unknown. Methods Transcriptomic analysis was performed to identify dysregulated lncRNAs in ESCC tissue samples. The high expression of LINC00680 in ESCC was validated by RT-qPCR, and the oncogenic functions of LINC00680 was investigated by cell proliferation, colony formation, migration and invasion assays in ESCC cells in vitro and xenografts derived from ESCC cells in mice. RNA-seq, competitive endogenous RNA (ceRNA) network analysis, and luciferase reporter assays were carried out to identify LINC00680 target genes and the microRNAs (miRNAs) bound to LINC00680. Antisense oligonucleotides (ASOs) were used for in vivo treatment. Results Transcriptome profiling revealed that a large number of lncRNAs was dysregulated in ESCC tissues. Notably, LINC00680 was highly expressed, and upregulation of LINC00680 was associated with large tumor size, advanced tumor stage, and poor prognosis. Functionally, knockdown of LINC00680 restrained ESCC cell proliferation, colony formation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, LINC00680 was found to act as a ceRNA by sponging miR-423-5p to regulate PAK6 (p21-activated kinase 6) expression in ESCC cells. The cell viability and motility inhibition induced by LINC00680 knockdown was significantly reversed upon PAK6 restoration and miR-423-5p inhibition. Furthermore, ASO targeting LINC00680 substantially suppressed ESCC both in vitro and in vivo. Conclusions An oncogenic lncRNA, LINC00680, was identified in ESCC, which functions as a ceRNA by sponging miR-423-5p to promote PAK6 expression and ESCC. LINC00680/miR-423-5p/PAK6 axis may serve as promising diagnostic and prognostic biomarkers and therapeutic targets for ESCC.

show abstract

“…In addition, studies have shown that KDR can serve as an independent prognostic biomarker in patients with unresectable HCC (21). AKT3 is an adverse prognostic factor in patients with HCC (22), and activation of AKT3 promotes HCC stem cell properties and reduces chemosensitivity (23). In addition, KIAA1429 is significantly overexpressed in HCC tissues and is associated with poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Screening potential prognostic biomarkers for portal vein emboli in patients with hepatocellular carcinoma

Zhou

Fang

2021

J Gastrointest Oncol

View full text Add to dashboard Cite

Background: The formation of portal vein tumor thrombus (PVTT) is closely related to the prognosis of patients with hepatocellular carcinoma (HCC). However, the mechanisms by which PVTTs form and the biomarkers involved are still little understood. Methods:The Genome Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to obtain transcriptome data from normal tissue, HCC tissue, primary tumors (PTs) of HCC, and paired PVTT tissue. Differentially expressed genes (DEGs) in PTs and PVTTs were analyzed. The differentially expressed immune genes were further investigated in terms of their prognostic significance, immune infiltration, function. Finally, we explored the relationship between risk scores and drug sensitivity based on the R package.Results: In the two datasets, there were 458 DEGs identified in the PT and PVTT tissues, of which, 58 were immune-related genes. The differentially expressed immune genes may promote the progression of PVTT by participating in the regulation of non-cellular components such as the extracellular matrix, inflammatory factors, and chemokines. Furthermore, the immune genes KDR, AKT3, FCGR2B, KIAA1429, and TPT1 were correlated with the prognosis of HCC in patients with PVTT. Using this data, a model was constructed to predict the prognosis of patients, thus allowing for the identification of high-and low-risk patients.Conclusions: This study demonstrated that immune-related genes may be involved in the regulation of the extracellular matrix and acellular components, and subsequently, in the formation of PVTT. These five genes KDR, AKT3, FCGR2B, KIAA1429, and TPT1 may be potential prognostic biomarkers and treatment targets for HCC patients with PVTT.

show abstract

LINC00680 enhances hepatocellular carcinoma stemness behavior and chemoresistance by sponging miR-568 to upregulate AKT3

Cited by 33 publications

References 36 publications

TFAP2C-Mediated lncRNA PCAT1 Inhibits Ferroptosis in Docetaxel-Resistant Prostate Cancer Through c-Myc/miR-25-3p/SLC7A11 Signaling

TFAP2C-Mediated lncRNA PCAT1 Inhibits Ferroptosis in Docetaxel-Resistant Prostate Cancer Through c-Myc/miR-25-3p/SLC7A11 Signaling

Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis

Screening potential prognostic biomarkers for portal vein emboli in patients with hepatocellular carcinoma

Contact Info

Product

Resources

About