FEZF1-AS1: a novel vital oncogenic lncRNA in multiple human malignancies

AbstractLong noncoding RNAs (LncRNAs) refer to the RNA with a length of >200 nucleotides, which lack or have no open reading coding frame and have higher tissue and organ specificity compared with the protein coding genes. A surging number of studies have shown that lncRNA is involved in numerous essential regulatory processes, such as X chromosome silencing, genomic imprinting, chromatin modification, transcriptional activation, transcriptional interference and nuclear transport, which are closely related to the occurrence and development of human malignancies. FEZ family Zinc Finger 1-Antisense RNA 1 (FEZF1-AS1) of FEZ family is a recently discovered lncRNA. FEZF1-AS1 is highly expressed in pancreatic cancer, colorectal cancer, lung adenocarcinoma and other human malignancies, and is associated with poor prognosis. As an oncogene, it plays crucial role in the proliferation, migration, invasion and Warburg effect of various tumor cells. In addition, FEZF1-AS1 is also involved in the regulation of multiple signal pathways such as epithelial–mesenchymal transition (EMT), signal transducer and activator of transcription 3 (STAT3) and Wnt/ β-catenin. In this paper, the recent research progress of FEZF1-AS1 in tumorigenesis and development is reviewed systematically.

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Upregulation of LINC01426 promotes the progression and stemness in lung adenocarcinoma by enhancing the level of SHH protein to activate the hedgehog pathway

Cell Death and Disease ◽

10.1038/s41419-021-03435-y ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Xiaoli Liu ◽

Zuwei Yin ◽

Linping Xu ◽

Huaimin Liu ◽

Lifeng Jiang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Bioinformatics Analysis ◽

Epithelial Mesenchymal Transition ◽

Mrna Level ◽

Hedgehog Pathway ◽

Biological Processes ◽

Protein Coding ◽

Mesenchymal Transition ◽

Functional Roles ◽

Rip Assay

AbstractLong noncoding RNAs (lncRNAs) play crucial roles in regulating a variety of biological processes in lung adenocarcinoma (LUAD). In our study, we mainly explored the functional roles of a novel lncRNA long intergenic non-protein coding RNA 1426 (LINC01426) in LUAD. We applied bioinformatics analysis to find the expression of LINC01426 was upregulated in LUAD tissue. Functionally, silencing of LINC01426 obviously suppressed the proliferation, migration, epithelial–mesenchymal transition (EMT), and stemness of LUAD cells. Then, we observed that LINC01426 functioned through the hedgehog pathway in LUAD. The effect of LINC01426 knockdown could be fully reversed by adding hedgehog pathway activator SAG. In addition, we proved that LINC01426 could not affect SHH transcription and its mRNA level. Pull-down sliver staining and RIP assay revealed that LINC01426 could interact with USP22. Ubiquitination assays manifested that LINC01426 and USP22 modulated SHH ubiquitination levels. Rescue assays verified that SHH overexpression rescued the cell growth, migration, and stemness suppressed by LINC01426 silencing. In conclusion, LINC01426 promotes LUAD progression by recruiting USP22 to stabilize SHH protein and thus activate the hedgehog pathway.

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NRF1-Mediated Oncogenic Reprogramming Drives Estrogen-Induced Breast Carcinogenesis

10.20944/preprints201809.0183.v1 ◽

2018 ◽

Author(s):

Jayanta Kumar Das ◽

Quentin Felty ◽

Robert Poppiti ◽

Robert M. Jackson ◽

Deodutta Roy

Keyword(s):

Breast Cancer ◽

Transcriptional Activation ◽

Epithelial Mesenchymal Transition ◽

Confocal Imaging ◽

Cancer Tissue ◽

Causative Role ◽

Dependent Manner ◽

Breast Carcinogenesis ◽

Human Breast Cancer Tissue ◽

Mesenchymal Transition

Transcription factor activity of the nuclear respiratory factor 1 protein (NRF1) is increased in breast cancer. Whether this gain of NRF1 activity is directly involved in breast cancer remains unknown. Herein, we report a novel oncogenic function of NRF1 supporting its causative role in breast cancer development and progression. The gain of NRF1 and/or treatment with 17β-estradiol (E2) produced heterogeneous breast cancer stem cells (BCSCs) composed of more than ten distinct cell sub-populations. Flow sorting combined with confocal imaging of markers for pluripotency, epithelial mesenchymal transition (EMT), and BCSCs phenotypically confirmed that the sub-populations of BCSCs arise from cell re-programming. Thus, we determined the molecular actions of NRF1 on its target gene CXCR4 because of its known role in the acquisition of BCSCs through EMT. CXCR4 was activated by NRF1 in a redox dependent manner during malignant transformation. NRF1-induced BCSCs were able to form xenograft tumors in vivo, while inhibiting transcription of CXCR4 prevented xenograft tumor growth. Consistent with our observation of NRF1 driven breast tumorigenesis in the experimental model, higher levels of NRF1 protein expression were also found in human breast cancer tissue specimens. This highly novel role of NRF1 in the stochastic acquisition of BCSCs and their progression to a malignant phenotype may open an entirely new research direction targeting NRF1 signaling in invasive breast cancer. Additionally, the discovery of targeting transcriptional activation of CXCR4 to inhibit NRF1-induced oncogenic transformation provides a mechanistic explanation for estrogen-dependent breast carcinogenesis and opens the new avenues for mechanistic therapeutic strategy against breast cancer.

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Biological functions and clinical significance of long noncoding RNAs in bladder cancer

Cell Death Discovery ◽

10.1038/s41420-021-00665-z ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yan Zhang ◽

Xianwu Chen ◽

Juntao Lin ◽

Xiaodong Jin

Keyword(s):

Bladder Cancer ◽

Clinical Significance ◽

Noncoding Rna ◽

Epithelial Mesenchymal Transition ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Research Progress ◽

High Morbidity ◽

Biological Functions ◽

Mesenchymal Transition

AbstractBladder cancer (BCa) is one of the 10 most common cancers with high morbidity and mortality worldwide. Long noncoding RNAs (lncRNAs), a large class of noncoding RNA transcripts, consist of more than 200 nucleotides and play a significant role in the regulation of molecular interactions and cellular pathways during the occurrence and development of various cancers. In recent years, with the rapid advancement of high-throughput gene sequencing technology, several differentially expressed lncRNAs have been discovered in BCa, and their functions have been proven to have an impact on BCa development, such as cell growth and proliferation, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and drug-resistance. Furthermore, evidence suggests that lncRNAs are significantly associated with BCa patients’ clinicopathological characteristics, especially tumor grade, TNM stage, and clinical progression stage. In addition, lncRNAs have the potential to more accurately predict BCa patient prognosis, suggesting their potential as diagnostic and prognostic biomarkers for BCa patients in the future. In this review, we briefly summarize and discuss recent research progress on BCa-associated lncRNAs, while focusing on their biological functions and mechanisms, clinical significance, and targeted therapy in BCa oncogenesis and malignant progression.

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Epithelial-Mesenchymal Transition Induces GSDME Transcriptional Activation for Inflammatory Pyroptosis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.781365 ◽

2021 ◽

Vol 9 ◽

Author(s):

Chenqiang Jia ◽

Zhuqing Zhang ◽

Jun Tang ◽

Mei-Chun Cai ◽

Jingyu Zang ◽

...

Keyword(s):

Cell Death ◽

Transcriptional Activation ◽

Promoter Region ◽

Drug Exposure ◽

Epithelial Mesenchymal Transition ◽

Experimental Models ◽

Cytokine Release ◽

Functional Importance ◽

Bioinformatics Analyses ◽

Mesenchymal Transition

GSDME is a newly recognized executor of cellular pyroptosis, and has been recently implicated in tumor growth and immunity. However, knowledge about the molecular regulators underlying GSDME abundance remains limited. Here, we performed integrative bioinformatics analyses and identified that epithelial-mesenchymal transition (EMT) gene signatures exhibited positive correlation with GSDME levels across human cancers. A causal role was supported by the observation that EMT dictated GSDME reversible upregulation in multiple experimental models. Mechanistically, transcriptional activation of GSDME was directly driven by core EMT-activating transcription factors ZEB1/2, which bound to the GSDME promoter region. Of functional importance, elevated GSDME in mesenchymally transdifferentiated derivatives underwent proteolytic cleavage upon antineoplastic drug exposure, leading to pyroptotic cell death and consequent cytokine release. Taken together, our findings pinpointed a key transcriptional machinery controlling GSDME expression and indicated potential therapeutic avenues to exploit GSDME-mediated inflammatory pyroptosis for the treatment of mesenchymal malignancies.

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Long Intergenic Non-Protein Coding RNA 1089 Suppresses Cell Proliferation and Metastasis in Gastric Cancer by Regulating miRNA-27a-3p/Epithelial–Mesenchymal Transition (EMT) Axis

Cancer Management and Research ◽

10.2147/cmar.s254064 ◽

2020 ◽

Vol Volume 12 ◽

pp. 5587-5596

Author(s):

Feng Yang ◽

Xiaoting Chen ◽

Xiyao Li ◽

Jianhua Chen ◽

Yuxin Tang ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Epithelial Mesenchymal Transition ◽

Protein Coding ◽

Mesenchymal Transition ◽

Proliferation And Metastasis ◽

Cell Proliferation And Metastasis

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Interplay between miRNAs and host genes and their role in cancer

Briefings in Functional Genomics ◽

10.1093/bfgp/elz002 ◽

2019 ◽

Vol 18 (4) ◽

pp. 255-266 ◽

Cited By ~ 16

Author(s):

Baohong Liu ◽

Yu Shyr ◽

Jianping Cai ◽

Qi Liu

Keyword(s):

Tumor Suppressors ◽

Target Genes ◽

Epithelial Mesenchymal Transition ◽

Fine Tuning ◽

Data Sets ◽

Protein Coding ◽

Mesenchymal Transition ◽

Damage Repair ◽

Cancer Types ◽

Host Genes

Abstract MicroRNAs (miRNAs) are small endogenous non-coding functional RNAs that post-transcriptionally regulate gene expression. They play essential roles in nearly all biological processes including cell development and differentiation, DNA damage repair, cell death as well as intercellular communication. They are highly involved in cancer, acting as tumor suppressors and/or promoters to modulate cell proliferation, epithelial-mesenchymal transition and tumor invasion and metastasis. Recent studies have shown that more than half of miRNAs are located within protein-coding or non-coding genes. Intragenic miRNAs and their host genes either share the promoter or have independent transcription. Meanwhile, miRNAs work as partners or antagonists of their host genes by fine-tuning their target genes functionally associated with host genes. This review outlined the complicated relationship between intragenic miRNAs and host genes. Focusing on miRNAs known as oncogenes or tumor suppressors in specific cancer types, it studied co-expression relationships between these miRNAs and host genes in the cancer types using TCGA data sets, which validated previous findings and revealed common, tumor-specific and even subtype-specific patterns. These observations will help understand the function of intragenic miRNAs and further develop miRNA therapeutics in cancer.

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Research Progress of Drug Prophylaxis for Lens Capsule Opacification after Cataract Surgery

Journal of Ophthalmology ◽

10.1155/2020/2181685 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Rong-Pei Zhang ◽

Zheng-Gao Xie

Keyword(s):

Cataract Surgery ◽

Epithelial Mesenchymal Transition ◽

Lens Capsule ◽

Research Progress ◽

Anterior Capsule ◽

Mesenchymal Transition ◽

Standard Operation ◽

Operation Procedure ◽

The Common ◽

Drug Prophylaxis

Phacoemulsification combined with intraocular lens (IOL) implantation is the international standard operation procedure for cataract and has been generalized worldwide. However, lens capsule opacification, one of the common complications after cataract surgery, impacts the recovery of patients’ visual function to a large extent. Lens capsule opacification has two types, anterior capsule opacification (ACO) and posterior capsule opacification (PCO), according to the location. There is not an accepted approach to treat ACO. Nd : YAG laser capsulotomy, the common treatment of PCO, can effectively improve the vision, but may cause a series of complications and is inappropriate for children who are too young to cooperate with this treatment. It is generally known that the responses of lens epithelial cells (LECs) after cataract surgery, including cell proliferation, migration, and epithelial-mesenchymal transition (EMT), play a key role in the pathogenesis of lens capsule opacification. Scholars found that substantial drugs can reduce the occurrence of lens capsule opacification by inhibiting, clearing, or killing LECs, and made great efforts as well as innovations on the exploration of drug species or modes of administration. This article is a systematic interpretation and elaboration about how to prevent lens capsule opacification after cataract surgery via different drugs.

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Roles of MicroRNA-34a in Epithelial to Mesenchymal Transition, Competing Endogenous RNA Sponging and Its Therapeutic Potential

International Journal of Molecular Sciences ◽

10.3390/ijms20040861 ◽

2019 ◽

Vol 20 (4) ◽

pp. 861 ◽

Cited By ~ 9

Author(s):

Dongsong Nie ◽

Jiewen Fu ◽

Hanchun Chen ◽

Jingliang Cheng ◽

Junjiang Fu

Keyword(s):

Cancer Therapy ◽

Cancer Progression ◽

Noncoding Rna ◽

Epithelial To Mesenchymal Transition ◽

Epithelial Mesenchymal Transition ◽

Therapeutic Potential ◽

Circular Rna ◽

Signal Pathways ◽

Competing Endogenous Rna ◽

Mesenchymal Transition

MicroRNA-34a (miR-34a), a tumor suppressor, has been reported to be dysregulated in various human cancers. MiR-34a is involves in certain epithelial-mesenchymal transition (EMT)-associated signal pathways to repress tumorigenesis, cancer progression, and metastasis. Due to the particularity of miR-34 family in tumor-associated EMT, the significance of miR-34a is being increasingly recognized. Competing endogenous RNA (ceRNA) is a novel concept involving mRNA, circular RNA, pseudogene transcript, and long noncoding RNA regulating each other’s expressions using microRNA response elements to compete for the binding of microRNAs. Studies showed that miR-34a is efficient for cancer therapy. Here, we provide an overview of the function of miR-34a in tumor-associated EMT. ceRNA hypothesis plays an important role in miR-34a regulation in EMT, cancer progression, and metastasis. Its potential roles and challenges as a microRNA therapeutic candidate are discussed. As the negative effect on cancer progression, miR-34a should play crucial roles in clinical diagnosis and cancer therapy.

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