Ultrasound-Targeted Microbubble Destruction-Mediated Downregulation of EZH2 Inhibits Stemness and Epithelial-Mesenchymal Transition of Liver Cancer Stem Cells

Wu, Jie; Sun, Lulu; Liu, Tingting; Dong, Gang

doi:10.2147/ott.s269589

Cited by 7 publications

(6 citation statements)

References 41 publications

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“…Such interactions are in favor of cancer metastasis. EZH2 upregulation can promote cancer metastasis via EMT induction [ 279 ]. The lncRNA taurine upregulated gene 1 (TUG1) cooperates with EZH2 to down-regulate miRNA-382 and aid in sponging, leading to EMT induction and pancreatic cancer invasion [ 280 ].…”

Section: Non-coding Rnas and Ezh2 Signalingmentioning

confidence: 99%

The long and short non-coding RNAs modulating EZH2 signaling in cancer

et al. 2022

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Non-coding RNAs (ncRNAs) are a large family of RNA molecules with no capability in encoding proteins. However, they participate in developmental and biological processes and their abnormal expression affects cancer progression. These RNA molecules can function as upstream mediators of different signaling pathways and enhancer of zeste homolog 2 (EZH2) is among them. Briefly, EZH2 belongs to PRCs family and can exert functional roles in cells due to its methyltransferase activity. EZH2 affects gene expression via inducing H3K27me3. In the present review, our aim is to provide a mechanistic discussion of ncRNAs role in regulating EZH2 expression in different cancers. MiRNAs can dually induce/inhibit EZH2 in cancer cells to affect downstream targets such as Wnt, STAT3 and EMT. Furthermore, miRNAs can regulate therapy response of cancer cells via affecting EZH2 signaling. It is noteworthy that EZH2 can reduce miRNA expression by binding to promoter and exerting its methyltransferase activity. Small-interfering RNA (siRNA) and short-hairpin RNA (shRNA) are synthetic, short ncRNAs capable of reducing EZH2 expression and suppressing cancer progression. LncRNAs mainly regulate EZH2 expression via targeting miRNAs. Furthermore, lncRNAs induce EZH2 by modulating miRNA expression. Circular RNAs (CircRNAs), like lncRNAs, affect EZH2 expression via targeting miRNAs. These areas are discussed in the present review with a focus on molecular pathways leading to clinical translation.

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Section: Non-coding Rnas and Ezh2 Signalingmentioning

confidence: 99%

The long and short non-coding RNAs modulating EZH2 signaling in cancer

et al. 2022

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“…The results showed that the positive expression rate of EZH2 in observation group 1 (75.95%) was higher than that in observation group 2 and control group (15.19% and 10.26%), suggesting that abnormal expression of EZH2 was related to the occurrence of small liver cancer. Studies suggested that EZH2 is highly expressed in small liver cancer, which affects the survival rate of patients [ 36 ]. Several studies pointed out that EZH2 is significantly ( P < 0.05) expressed in human hepatocellular carcinoma tissues and cell lines.…”

Section: Discussionmentioning

confidence: 99%

Multimodal Imaging under Artificial Intelligence Algorithm for the Diagnosis of Liver Cancer and Its Relationship with Expressions of EZH2 and p57

Zhang¹,

Cui

Wan³

et al. 2022

Computational Intelligence and Neuroscience

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Objective. It aimed to explore the diagnostic efficacy of multimodal ultrasound images based on mask region with convolutional neural network (M-RCNN) segmentation algorithm for small liver cancer and analyze the expression of zeste gene enhancer homolog 2 (EZH2) and p57 (P57 Kip2) genes in cancer cells. Methods. A total of 100 patients suspected of small liver cancer were randomly divided into Doppler group (color Doppler ultrasound examination), contrast group (contrast ultrasound examination), elastic group (ultrasound elastography examination), and multimodal group (combined examination of the three methods), with 25 patients in each group. Images were processed by the M-RCNN segmentation algorithm. The results of the pathological biopsy were used to evaluate the diagnostic efficacy of the four methods. The liver tissues were then extracted and divided into observation group 1 (lesion tissue specimen), observation group 2 (liver tissue around cancer lesion), and control group (normal liver tissue), and the expression activities of EZH2 and p57 genes in the three groups were analyzed. Results. The accuracy of M-RCNN (97.23%) and average precision (AP) (71.90%) were higher than other methods ( P < 0.05 ). Sensitivity (88.87%), specific degree of consistency (90.91%), accuracy (89.47%), and consistence (0.68) of the multimodal group were better than the other three groups ( P < 0.05 ). Low and medium differentiated cancer tissues had an irregular shape, unclear boundary, uneven internal echo, unchanged/enhanced posterior echo, blood flow level 1∼2, elastic score 4∼5, and enhancement mode fast in and fast out. The positive expression rate of EZH2 in observation group 1 (75.95%) was higher than that in the other two groups, the positive expression rate of p57 in observation group 1 (80.79%) was lower than that in the other two groups, and the positive expression rate of p57 in the highly differentiated cancer foci (80.79%) was significantly lower than that in the middle and low differentiated cancer foci ( P < 0.05 ). Conclusions. M-RCNN segmentation algorithm had a better segmentation effect. Multimodal ultrasound had a good effect on the benign and malignant diagnosis of small liver cancer and had a high clinical application value. The high expression of EZH2 and the decreased expression of p57 can promote the occurrence of small hepatocellular carcinoma, and the deficiency of the P57 gene was related to the low differentiation of cancer cells.

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“…Subcutaneous tumors were excised and weighed. All mice were dissected and tumor tissues were collected for subsequent experimental analysis [22,23].…”

Section: Animal Model Constructionmentioning

confidence: 99%

The role of LINC01419 in regulating the cell stemness in lung adenocarcinoma through recruiting EZH2 and regulating FBP1 expression

Tang

Zhou

2022

Biol Direct

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Background Recent years have witnessed a growing academic interest in the effects of lncRNAs on tumors. LINC01419 is found to facilitate proliferation and metastasis of lung adenocarcinoma (LUAD) cells, but there is a great deal of uncertainty about how LINC01419 works on LUAD cell stemness. For this reason, the focus of this research is centered on the regulatory impact of LINC01419 on LUAD cell stemness. Methods For the detection of the expression level of LINC01419 in LUAD, qRT-PCR was performed. And how oe-LINC01419 and sh-LINC01419 affected LUAD cell proliferation as well as stem cell sphere-formation were examined by CCK-8 and cell sphere-forming assays. In addition, whether LINC01419 could recruit EZH2 and regulate FBP1 expression were determined by bioinformatics analysis, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP). Western blot was utilized to detect the protein expression levels of FBP1, CD44, CD133, and ALDH-1 as well. Results On the basis of the findings from those assays, an up-regulation of LINC01419 level was demonstrated in LUAD cell lines, and a remarkable upregulation of it in CD44 + LUAD cells. In LUAD cells, proliferation and stem cell sphere-formation that were attenuated by LINC01419 knockdown were discovered to be facilitated by LINC01419 overexpression. And a binding relationship between LINC01419 and EZH2 was determined by RIP assay. Besides, EZH2 was capable of binding to FBP1 promoter region, as found by ChIP-PCR assay. Finally, it was demonstrated by in vitro experiments that LINC01419 could inhibit FBP1 expression by recruiting EZH2, resulting in promotion of LUAD cell proliferation and stemness. Significance To summarize, our findings demonstrate a cancer-promoting role of LINC01419 in LUAD. LINC01419, by recruiting EZH2 and regulating FBP1 expression, contributes to LUAD cell stemness. According to these findings, the potential of LINC01419 to be the target for LUAD treatment is hence determined, which also adds more possibility to the enrichment of therapeutic strategies for lung cancer stem cells.

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Ultrasound-Targeted Microbubble Destruction-Mediated Downregulation of EZH2 Inhibits Stemness and Epithelial-Mesenchymal Transition of Liver Cancer Stem Cells

Cited by 7 publications

References 41 publications

The long and short non-coding RNAs modulating EZH2 signaling in cancer

The long and short non-coding RNAs modulating EZH2 signaling in cancer

Multimodal Imaging under Artificial Intelligence Algorithm for the Diagnosis of Liver Cancer and Its Relationship with Expressions of EZH2 and p57

The role of LINC01419 in regulating the cell stemness in lung adenocarcinoma through recruiting EZH2 and regulating FBP1 expression

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