The lncRNA HOTAIR: a pleiotropic regulator of epithelial cell plasticity DOI Creative Commons
Laura Amicone, Alessandra Marchetti, Carla Cicchini

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: June 13, 2023

The epithelial-to-mesenchymal transition (EMT) is a trans-differentiation process that endows epithelial cells with mesenchymal properties, including motility and invasion capacity; therefore, its aberrant reactivation in cancerous represents critical step to gain metastatic phenotype. EMT dynamic program of cell plasticity; many partial states can be, indeed, encountered the full inverse mesenchymal-to-epithelial (MET) appears fundamental colonize distant secondary sites. EMT/MET dynamics granted by fine modulation gene expression response intrinsic extrinsic signals. In this complex scenario, long non-coding RNAs (lncRNAs) emerged as players. This review specifically focuses on lncRNA HOTAIR, master regulator plasticity tumors. Molecular mechanisms controlling differentiated well trans-differentiated are highlighted here. Moreover, current knowledge about HOTAIR pleiotropic functions regulation both protein activities described. Furthermore, relevance specific targeting challenges exploiting for therapeutic approaches counteract discussed.

Language: Английский

Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer DOI Creative Commons
Hui Yang, Yiren Hu, Mingzhe Weng

et al.

Journal of Advanced Research, Journal Year: 2021, Volume and Issue: 37, P. 91 - 106

Published: Oct. 6, 2021

Tumors are usually refractory to anti-cancer therapeutics under hypoxic conditions. However, the underlying molecular mechanism remains be elucidated. Our study intended identify hypoxia inducible lncRNAs and their biological function in gastric cancer (GC). Differentially expressed were determined by microarray analysis between GC cells exposed (1% O2) normoxia (21% for 24 h. The expression level of CBSLR was manipulated several cell lines perform analyses both vitro vivo. We identified a hypoxia-induced lncRNA-CBSLR that protected from ferroptosis, leading chem-resistance. Mechanically, interacted with YTHDF2 form CBSLR/YTHDF2/CBS signaling axis decreased stability CBS mRNA enhancing binding m6A-modified coding sequence (CDS) mRNA. Furthermore, levels, methylation ACSL4 protein reduced, polyubiquitination degradation ACSL4. This, turn, pro-ferroptosis phosphatidylethanolamine (PE) (18:0/20:4) PE (18:0/22:4) content contributed ferroptosis resistance. Notably, is upregulated, whereas downregulated tissues compared matched normal tissues; patients high CBSLR/low levels have worse clinical outcome poorer response chemotherapy. reveals novel how HIF1α/CBSLR modulates ferroptosis/chemoresistance GC, illuminating potential therapeutic targets tumors.

Language: Английский

Citations

180
Long non-coding RNAs in the doxorubicin resistance of cancer cells DOI

Saeed Ashrafizaveh,

Milad Ashrafizadeh, Ali Zarrabi

et al.

Cancer Letters, Journal Year: 2021, Volume and Issue: 508, P. 104 - 114

Published: March 23, 2021

Language: Английский

Citations

156
Molecular Landscape of LncRNAs in Prostate Cancer: A focus on pathways and therapeutic targets for intervention DOI Creative Commons
Sepideh Mirzaei, Mahshid Deldar Abad Paskeh,

Elena Okina

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: July 1, 2022

Abstract Background One of the most malignant tumors in men is prostate cancer that still incurable due to its heterogenous and progressive natures. Genetic epigenetic changes play significant roles development. The RNA molecules with more than 200 nucleotides length are known as lncRNAs these factors do not encode protein. They regulate gene expression at transcriptional, post-transcriptional levels. LncRNAs vital biological functions cells pathological events, hence their undergoes dysregulation. Aim review role alterations development emphasized here. Therefore, were chosen for this purpose level interaction other signaling networks progression examined. Key scientific concepts aberrant has been well-documented rate tumor regulated via affecting STAT3, NF-κB, Wnt, PI3K/Akt PTEN, among molecular pathways. Furthermore, radio-resistance chemo-resistance features cells. Overexpression tumor-promoting such HOXD-AS1 CCAT1 can result drug resistance. Besides, induce immune evasion upregulating PD-1. Pharmacological compounds quercetin curcumin have applied targeting lncRNAs. siRNA tool reduce thereby suppressing progression. Prognosis diagnosis clinical course be evaluated by exosomal lncRNA-p21 investigated serum patients a reliable biomarker.

Language: Английский

Citations

126
Characteristics of the cancer stem cell niche and therapeutic strategies DOI Creative Commons
Feng Ju, Manar Atyah,

Nellie Horstmann

et al.

Stem Cell Research & Therapy, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 3, 2022

Distinct regions harboring cancer stem cells (CSCs) have been identified within the microenvironment of various tumors, and as in case their healthy counterparts, these anatomical are termed "niche." Thus far, a large volume studies shown that CSC niches take part maintenance, regulation renewal, differentiation plasticity CSCs. In this review, we summarize discuss latest findings regarding niche morphology, physical terrain, main signaling pathways interactions them. The cellular molecular components CSCs also involve genetic epigenetic modulations mediate support ultimately leading to progression. It suggests crosstalk between plays an important role therapy resistance recurrence. addition, updated diverse therapeutic strategies different cancers basic research clinical trials review. Understanding complex heterogeneity is necessary pre-requisite for designing superior target CSC-specific factors and/or niche.

Language: Английский

Citations

78
Cancer-associated fibroblasts facilitate premetastatic niche formation through lncRNA SNHG5-mediated angiogenesis and vascular permeability in breast cancer DOI Creative Commons
Huan Zeng, Yixuan Hou, Xinyue Zhou

et al.

Theranostics, Journal Year: 2022, Volume and Issue: 12(17), P. 7351 - 7370

Published: Jan. 1, 2022

Background: Metastasis is the leading cause of death in patients with breast cancer (BC). Primary tumors create a premetastatic niche (PMN) secondary organs for subsequent metastases. Cancer-associated fibroblasts (CAFs) are predominant stromal component tumor microenvironment and serve as major contributor to metastasis. However, function mechanism primary CAFs remain unclear BC. Methods: We investigated expression profiles lncRNAs pairs NFs derived from tissues using lncRNA microarray. The levels lncSNHG5, ZNF281, IGF2BP2, CCL2 CCL5 were assessed by qRT-PCR; protein related genes (e.g., CCL2, CCL5) analyzed western blotting and/or ELISA immortalized clinical samples. Tubule formation three-dimensional sprouting assays tissue fluorescence staining conducted investigate angiogenesis. In vitro permeability assays, trans-endothelial invasion vivo examine vascular permeability. regulatory lncSNHG5 was RNA sequencing, fluorescent situ hybridization, cellular fractionation assay, mass spectrometry, pull-down, immunoprecipitation, gene-specific m6A chromatin dual luciferase reporter assay actinomycin D treatment NFs. Results: LncSNHG5 highly expressed played an essential role promoting angiogenesis leakiness through regulation ZNF281 CAFs. enhanced mRNA stability binding reader IGF2BP2. Enhanced transcriptionally regulated activate P38 MAPK signaling endothelial cells. High associated metastasis poor prognosis BC patients. inhibitors RS102895, marasviroc cenicriviroc inhibited PMN blocking CCL2/CCR2 CCL5/CCR5. lncSNHG5-ZNF281-CCL2/CCL5 axis plays inducing promote Conclusions: Our work demonstrates that its downstream ZNF281-CCL2/CCL5 play crucial may potential targets diagnosis

Language: Английский

Citations

74
Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer DOI Creative Commons
Zhen Zeng,

Minyang Fu,

Yuan Hu

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 18, 2023

Abstract Cancer stem cells (CSCs), initially identified in leukemia 1994, constitute a distinct subset of tumor characterized by surface markers such as CD133, CD44, and ALDH. Their behavior is regulated through complex interplay networks, including transcriptional, post-transcriptional, epigenetic, microenvironment (TME), epithelial-mesenchymal transition (EMT) factors. Numerous signaling pathways were found to be involved the regulatory network CSCs. The maintenance CSC characteristics plays pivotal role driving CSC-associated metastasis conferring resistance therapy. Consequently, CSCs have emerged promising targets cancer treatment. To date, researchers developed several anticancer agents tailored specifically target CSCs, with some these treatment strategies currently undergoing preclinical or clinical trials. In this review, we outline origin biological explore networks governing discuss implicated investigate influential factors contributing therapy Finally, offer insights into designed eliminate

Language: Английский

Citations

64
Predict lncRNA-drug associations based on graph neural network DOI Creative Commons
Peng Xu, Chuchu Li, Jiaqi Yuan

et al.

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: April 26, 2024

LncRNAs are an essential type of non-coding RNAs, which have been reported to be involved in various human pathological conditions. Increasing evidence suggests that drugs can regulate lncRNAs expression, makes it possible develop as therapeutic targets. Thus, developing

Language: Английский

Citations

27
lncRNA and breast cancer: Progress from identifying mechanisms to challenges and opportunities of clinical treatment DOI Creative Commons
Xin Jin, Wei Du, Wentao Huang

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2021, Volume and Issue: 25, P. 613 - 637

Published: Aug. 19, 2021

Breast cancer is a malignant tumor that has high mortality rate and mostly occurs in women. Although significant progress been made the implementation of personalized treatment strategies for molecular subtypes breast cancer, therapeutic response often not satisfactory. Studies have reported long non-coding RNAs (lncRNAs) are abnormally expressed closely related to occurrence development cancer. In addition, tissue cell-type specificity makes lncRNAs particularly attractive as diagnostic biomarkers, prognostic factors, specific targets. Therefore, an in-depth understanding regulatory mechanisms essential developing new strategies. this review, we systematically elucidate general characteristics, potential mechanisms, targeted therapy discuss emerging functions Additionally, also highlight advantages challenges using biomarkers diagnosis or targets drug resistance present future perspectives clinical practice.

Language: Английский

Citations

81
LncTarD 2.0: an updated comprehensive database for experimentally-supported functional lncRNA–target regulations in human diseases DOI Creative Commons

Hongying Zhao,

Xiangzhe Yin,

Haotian Xu

et al.

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 51(D1), P. D199 - D207

Published: Nov. 2, 2022

Abstract An updated LncTarD 2.0 database provides a comprehensive resource on key lncRNA–target regulations, their influenced functions and lncRNA-mediated regulatory mechanisms in human diseases. is freely available at (http://bio-bigdata.hrbmu.edu.cn/LncTarD or https://lnctard.bio-database.com/). was with several new features, including (i) an increased number of disease-associated lncRNA entries, where the current release 8360 419 disease subtypes 1355 lncRNAs; (ii) predicted 3312 out regulations as potential diagnostic therapeutic biomarkers circulating tumor cells (CTCs); (iii) addition 536 new, experimentally supported that modulate properties cancer stem cells; (iv) clinical application section 2894 for application. Importantly, RNA-seq/microarray single-cell web tools customizable analysis visualization tool used to mining both tissue samples CTCs blood samples. The provide annotation from perspectives pan-cancer cancer-specific level. will be useful investigation deregulation disease.

Language: Английский

Citations

40
Disheveled3 enhanced EMT and cancer stem-like cells properties via Wnt/β-catenin/c-Myc/SOX2 pathway in colorectal cancer DOI Creative Commons
Zhengguang Li, Zhirong Yang, Wei Liu

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 5, 2023

Epithelial-to-mesenchymal transition (EMT) and cancer stem-like cells (CSLCs) play crucial role in tumor metastasis drug-resistance. Disheveled3 (DVL3) is involved malignant behaviors of cancer. However, the potential mechanism DVL3 remain elusive EMT CSLCs colorectal (CRC).

Language: Английский

Citations

31