Tumor-suppressing miR-141 gene complex-loaded tissue-adhesive glue for the locoregional treatment of hepatocellular carcinoma

Kim, Minkyoung; Moon, Young-Ah; Song, Chung Kil; Baskaran, Rengarajan; Bae, Sijeong; Yang, Su‐Geun

doi:10.7150/thno.24056

Cited by 19 publications

(14 citation statements)

References 38 publications

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“…miRNA deregulation and dysfunction play a significant role in human cancer pathogenesis 4-6. Mature miRNAs, a class of ~22 nucleotide-long RNA molecules, are cleaved from long hairpin miRNA precursors by the cytoplasmic RNase III, Dicer.…”

Section: Introductionmentioning

confidence: 99%

UBE2C, Directly Targeted by miR-548e-5p, Increases the Cellular Growth and Invasive Abilities of Cancer Cells Interacting with the EMT Marker Protein Zinc Finger E-box Binding Homeobox 1/2 in NSCLC

Jin

Guo

et al. 2019

Theranostics

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Background: Recent evidence indicates that UBE2C participates in carcinogenesis by regulating the cell cycle, apoptosis, metastasis, and transcriptional processes. Additionally, miR-548e-5p dysregulation plays a vital role in tumor progression. However, the molecular mechanism via which UBE2C is directly targeted by miR-548-5p, resulting in increase in cellular growth and invasiveness of cancer cells, and its interactions with the epithelial-mesenchymal transition (EMT) marker protein ZEB1/2 in non-small cell lung cancer (NSCLC) is not understood. Methods: Expression of UBE2C and miR-548e-5p was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein level of UBE2C and ZEB1/2 was analyzed using western blotting and immunofluorescence staining. Cellular proliferation was detected using the cell counting kit 8 (CCK8) and 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Cell migration, invasion, and growth were analyzed using the wound healing and transwell assay. Promoter activity and transcription was analyzed using the luciferase reporter assay. Chromatin immunoprecipitation was used to detect binding of UBE2C to 5′UTR-ZEB1/2. Results: We observed that 4,5-ubiquitin-conjugating enzyme E2C ( UBE2C ) expression was higher in NSCLC tissue than in the adjacent normal tissue and was associated with increased cell proliferation and invasion. UBE2C enhanced NSCLC progression and metastasis by affecting the cell cycle and inhibiting apoptosis. We also observed that miR-548e-5p was significantly downregulated in lung cancer tissue specimens, which decreased the expression of its direct substrate, UBE2C . Moreover, miR-548e-5p overexpression and UBE2C under-expression significantly suppressed lung cancer cell proliferation, migration, and invasion. Luciferase reporter and chromatin immunoprecipitation assays indicated that miR-548e-5p directly binds to the 3′-UTR of UBE2C and decreases UBE2C mRNA expression. Furthermore, UBE2C knockdown downregulated the mesenchymal marker vimentin and upregulated the epithelial marker E-cadherin. Bioinformatics assays, coupled with western blotting and luciferase assays, revealed that UBE2C directly binds to the 5′-untranslated region (UTR) of the transcript of the E-cadherin repressor ZEB1/2 and promotes EMT in lung cancer cells. Conclusion: miR-548e-5p directly binds to the 3′-UTR of UBE2C and decreases UBE2C mRNA expression. UBE2C is an oncogene that promotes EMT in lung cancer cells by directly targeting the 5′-UTR of the transcript encoding the E-cadherin repressor ZEB1/2. miR-548e-5p, UBE2C, and ZEB1/2 constitute the miR-548e-5p-UBE2C-ZEB1/2 signal axis, which enhances cancer cell invasiveness by directly interacting with ...

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Section: Introductionmentioning

confidence: 99%

UBE2C, Directly Targeted by miR-548e-5p, Increases the Cellular Growth and Invasive Abilities of Cancer Cells Interacting with the EMT Marker Protein Zinc Finger E-box Binding Homeobox 1/2 in NSCLC

Jin

Guo

et al. 2019

Theranostics

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“…In addition, TM4SF1 was shown to increase E-cadherin expression through the AKT signaling pathway in pancreatic and colorectal cancers (Zheng B. et al, 2015;Xu D. et al, 2020). Kim et al (2018) demonstrated that miR-141 expression was related to TM4SF1 in pancreatic cancer, and upregulating miR-141, which decreased TM4SF1, reduced E-cadherin and VEGF-A to accelerate EMT in pancreatic cancer cells.…”

Section: Tm4sf1 Promotes Emtmentioning

confidence: 95%

Role of Transmembrane 4 L Six Family 1 in the Development and Progression of Cancer

Yang²,

Zheng

et al. 2020

Front. Mol. Biosci.

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Transmembrane 4 L six family 1 (TM4SF1) is a protein with four transmembrane domains that belongs to the transmembrane 4 L six family members (TM4SFs). Structurally, TM4SF1 consists of four transmembrane domains (TM1-4), N-and C-terminal intracellular domains, two extracellular domains, a smaller domain between TM1 and TM2, and a larger domain between TM3 and TM4. Within the cell, TM4SF1 is located at the cell surface where it transmits extracellular signals into the cytoplasm. TM4SF1 interacts with tetraspanins, integrin, receptor tyrosine kinases, and other proteins to form tetraspanin-enriched microdomains. This interaction affects the pro-migratory activity of the cells, and thus it plays important roles in the development and progression of cancer. TM4SF1 has been shown to be overexpressed in many malignant tumors, including gliomas; malignant melanomas; and liver, prostate, breast, pancreatic, bladder, colon, lung, gastric, ovarian, and thyroid cancers. TM4SF1 promotes the migration and invasion of cancer cells by inducing epithelial-mesenchymal transition, self-renewal ability, tumor angiogenesis, invadopodia formation, and regulating the related signaling pathway. TM4SF1 is an independent prognostic indicator and biomarker in several cancers. It also promotes drug resistance, which is a major cause of therapeutic failure. These characteristics make TM4SF1 an attractive target for antibody-based immunotherapy. Here, we review the many functions of TM4SF1 in malignant tumors, with the aim to understand the interaction between its expression and the biological behaviors of cancer and to supply a basis for exploring new therapeutic targets.

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“…Therefore, many vectors have been used to improve the stability of oligonucleotides. However, these drugs are di cult to achieve targeted drug delivery (18). We believe that miR-141-5p and si-hsa_circ_0063526 have the best therapeutic effect as an intraperitoneal injection (44).…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0063526 promotes the development of endometriosis by sponging miRNA-141-5p

Wei¹,

Zhang²,

Zhang³

et al. 2021

Preprint

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Background:Endometriosis can cause various social burdens. Abnormal circular RNAs level lead to changes of related gene expression, thereby mediating the occurrence and development of a series of diseases. The research of circRNA in endometriosis is still in its infancy. This study will explore the role of hsa_circ_0063526 with microRNA-141-5p in the development of endometriosis.Methods:The expression of genes was detected by RT-qPCR. Transwell, wound-healing, EdU assay were performed on endometriosis patient’s End1 / E6E7 cell. PCR and immunohistochemistry were used to detect the expression of candidate regulatory genes in ectopic lesions in endometriosis mice model.Results:The expression level of hsa_circ_0063526 in endometriosis patients’ ectopic tissue is higher than control(P <0.05), The expression levels of hsa_circ_0063526 and miRNA-141-5P in ectopic tissue of endometriosis were negatively correlated (P < 0.05).Knockdown hsa_circ_0063526 inhibited the invasion, metastasis, and proliferation ability of End1 / E6E7 cell. The inhibition of microRNA-141-5p can rescue this inhibitory effect (P <0.05). In-vivo experiments showed miR-141-5p and si-hsa_circ_0063526 treatment reduced the lesion size and regulated endometriosis genes.Conclusion:Hsa_circ_0063526 is probably involved in regulating the occurrence and development of endometriosis by sponging miR-141-5p. hsa_circ_0063526 and miR-141-5p are possible to become biomarkers and therapeutic targets for endometriosis.

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Tumor-suppressing miR-141 gene complex-loaded tissue-adhesive glue for the locoregional treatment of hepatocellular carcinoma

Cited by 19 publications

References 38 publications

UBE2C, Directly Targeted by miR-548e-5p, Increases the Cellular Growth and Invasive Abilities of Cancer Cells Interacting with the EMT Marker Protein Zinc Finger E-box Binding Homeobox 1/2 in NSCLC

UBE2C, Directly Targeted by miR-548e-5p, Increases the Cellular Growth and Invasive Abilities of Cancer Cells Interacting with the EMT Marker Protein Zinc Finger E-box Binding Homeobox 1/2 in NSCLC

Role of Transmembrane 4 L Six Family 1 in the Development and Progression of Cancer

Hsa_circ_0063526 promotes the development of endometriosis by sponging miRNA-141-5p

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