Exosomal Linc00969 induces trastuzumab resistance in breast cancer by increasing HER-2 protein expression and mRNA stability by binding to HUR

Breast Cancer Research, Journal Year: 2023, Volume and Issue: 25(1)

Published: Oct. 17, 2023

Breast cancer (BC) is the most common malignant disease in female patients worldwide. In HER-2+ BC patients, trastuzumab therapy associated with a better prognosis. However, many experience recurrence or metastasis because of resistance. The mechanisms underlying resistance remain unclear. Recently, substantial evidence has suggested that exosomes are drug resistance, and lncRNAs have attracted increasing attention due to their potential role regulation resistance.We collected from plasma without sequenced whole transcriptomes, identified differentially expressed lncRNAs, lncRNA Linc00969, which was overexpressed trastuzumab-resistant patients. Then, we established cell lines explored exosomal Linc00969 vitro vivo by silencing overexpressing performing series functional analyses. Furthermore, explore mechanism contributes measured changes HER-2, HUR autophagy-related protein expression levels after regulating expression. addition, investigated interaction between via pull-down RIP assays effect on HER-2 blocking HUR.We first found exosome-mediated transfer could disseminate BC. reduce enhance our results showed upregulate at level maintain stability mRNA binding HUR. Additionally, regulate inducing autophagy.In this study, induce HUR, might also be involved autophagy. Our elucidate novel new target for improving treatment

Language: Английский

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Breast Cancer Chemoresistance: Insights into the Regulatory Role of lncRNA

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15897 - 15897

Published: Nov. 2, 2023

Long noncoding RNAs (lncRNAs) are a subclass of composed more than 200 nucleotides without the ability to encode functional proteins. Given their involvement in critical cellular processes such as gene expression regulation, transcription, and translation, lncRNAs play significant role organism homeostasis. Breast cancer (BC) is second most common worldwide evidence has shown relationship between aberrant lncRNA BC development. One main obstacles control multidrug chemoresistance, which associated with deregulation multiple mechanisms efflux transporter activity, mitochondrial metabolism reprogramming, epigenetic regulation well apoptosis autophagy. Studies have large number pathways. However, underlying mechanism not clearly elucidated. In this review, we present principal chemoresistance that can be directly or indirectly regulated by lncRNA, highlighting importance controlling chemoresistance. Understanding these deep detail may interest clinical outcome patients could used therapeutic targets overcome therapy resistance.

Language: Английский

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The pivotal role of long non-coding RNAs as potential biomarkers and modulators of chemoresistance in ovarian cancer (OC)

Human Genetics, Journal Year: 2024, Volume and Issue: 143(2), P. 107 - 124

Published: Jan. 26, 2024

Language: Английский

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Prognostic and diagnostic values of non-coding RNAs as biomarkers for breast cancer: An umbrella review and pan-cancer analysis

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Jan. 16, 2023

Background: Breast cancer (BC) is the most common in women. The incidence and morbidity of BC are expected to rise rapidly. stage at which diagnosed has a significant impact on clinical outcomes. When detected early, an overall 5-year survival rate up 90% possible. Although numerous studies have been conducted assess prognostic diagnostic values non-coding RNAs (ncRNAs) breast cancer, their potential remains unclear. In this field study, there various systematic reviews meta-analysis that report volumes data. we tried collect all these order re-analyze data without any restriction or RNA type, make it as comprehensive Methods: Three databases, namely, PubMed, Scopus, Web Science (WoS), were searched find relevant studies. After thoroughly searching, screening titles, abstracts, full-text quality included assessed using AMSTAR tool. All required including hazard ratios (HRs), sensitivity (SENS), specificity (SPEC) extracted for further analysis, analyses carried out Stata. Results: part, our initial search three databases produced 10,548 articles, 58 current study. We correlation (ncRNA) expression with different outcomes patients: (OS) (HR = 1.521), disease-free (DFS) 1.33), recurrence-free (RFS) 1.66), progression-free (PFS) 1.71), metastasis-free (MFS) 0.90), disease-specific (DSS) 0.37). eliminating low-quality studies, results did not change significantly. 22 articles 30 datasets retrieved from 8,453 articles. was determined. bivariate random-effects models used value ncRNAs. area under curve (AUC) ncRNAs differentiated patients 0.88 (SENS: 80% SPEC: 82%). There no difference single combined patients. However, microRNAs (miRNAs) higher than long (lncRNAs). No evidence publication bias found Nine miRNAs, four lncRNAs, five gene targets showed OS RFS between normal based pan-cancer demonstrating value. Conclusion: present umbrella review ncRNAs, lncRNAs can be biomarkers patients, regardless sample sources, ethnicity subtype cancer.

Language: Английский

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Metformin and long non-coding RNAs in breast cancer

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

Published: Feb. 27, 2023

Abstract Breast cancer (BC) is the second most common and cause of death in women. In recent years many studies investigated association long non-coding RNAs (lncRNAs), as novel genetic factors, on BC risk, survival, clinical pathological features. Recent also roles metformin treatment firstline for type 2 diabetes (T2D) played lncRNAs expression/regulation or incidence, outcome, mortality separately. This comprehensive study aimed to review associated with features identify metformin-regulated their mechanisms action other types cancers. Finally, affects by regulating five BC-associated including GAS5, HOTAIR, MALAT1, H19, several molecular have been described this review. addition, cancers ten AC006160.1, Loc100506691, lncRNA-AF085935, SNHG7, HULC, UCA1, AFAP1-AS1, AC026904.1 described.

Language: Английский

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The current advances of lncRNAs in breast cancer immunobiology research

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: June 5, 2023

Breast cancer is the most frequently diagnosed malignancy and leading cause of cancer-related death in women worldwide. development progression are mainly associated with tumor-intrinsic alterations diverse genes signaling pathways tumor-extrinsic dysregulations linked to tumor immune microenvironment. Significantly, abnormal expression lncRNAs affects microenvironment characteristics modulates behavior different types, including breast cancer. In this review, we provide current advances about role as modulators antitumoral response cancer, well which potential biomarkers clinicopathological patients, suggesting that targets for immunotherapy

Language: Английский

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Functional interplay between long non-coding RNAs and Breast CSCs

Cancer Cell International, Journal Year: 2022, Volume and Issue: 22(1)

Published: July 21, 2022

Abstract Breast cancer (BC) represents aggressive affecting most women’s lives globally. Metastasis and recurrence are the two common factors in a breast patient's poor prognosis. Cancer stem cells (CSCs) tumor that able to self-renew differentiate, which is significant factor metastasis of cancer. Long non-coding RNAs (lncRNAs) describe group longer than 200 nucleotides do not have ability code for proteins. Some these lncRNAs can be mainly produced various tissues forms. In development spread malignancies, role influencing multiple signaling pathways positively or negatively, making them promise useful diagnostic prognostic markers treating disease guiding clinical therapy. However, it well known how interaction with CSCs will affect progression. Here, this review, we attempt summarize recent findings focus on cell self-renewal differentiation progression, as strategies challenges overcoming lncRNA's therapeutic resistance.

Language: Английский

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MALAT1-regulated gene expression profiling in lung cancer cell lines

BMC Cancer, Journal Year: 2023, Volume and Issue: 23(1)

Published: Sept. 4, 2023

Abstract Background Non-small cell lung cancer (NSCLC) is the most common type of and has a poor prognosis. Identifying biomarkers based on molecular mechanisms critical for early diagnosis, timely treatment, improved prognosis cancer. MALAT1 been reported to have overexpressed tumor-promoting functions in NSCLC. It proposed as potential biomarker diagnosis Therefore, this study was conducted profile changes gene expression according regulation NSCLC lines investigate correlation through bioinformatic analysis differentially expressed genes (DEGs). Methods levels were measured using RT-qPCR. The biological analyzed by counting, colony forming, wound-healing, Transwell invasion assays. In addition, profiling response knockdown transcriptome sequencing, regulated performed GO KEGG pathway enrichment analyses. Bioinformatic databases used overall survival analysis. Results Comparative versus MRC5 cells (a normal line) three showed that significantly higher cells. decreased survival, proliferation, migration, all lines. RNA-seq DEGs 198 upregulated 266 downregulated Survival these OncoLnc database resulted selection five DEGs, phosphoglycerate mutase 1 ( PGAM1 ), 4 PGAM4 nucleolar protein 6 NOL6 nucleosome assembly like 5 NAP1L5 sestrin1 SESN1 ). selected proved TNMplot database. Conclusion might function an oncogene enhances formation, invasion. analyses , which found be closely related patient tumorigenesis. We believe further investigation will provide valuable information oncogenic role

Language: Английский

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Attention Holistic Processing Multi-Channel Graph Transformer with Graph Residual Connections for Predicting lncRNA–Protein Interactions

Knowledge-Based Systems, Journal Year: 2025, Volume and Issue: 310, P. 112957 - 112957

Published: Jan. 5, 2025

Language: Английский

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LURAP1L-AS1 Long Noncoding RNA Promotes Breast Cancer Progression and Associates with Poor Prognosis

Non-coding RNA Research, Journal Year: 2025, Volume and Issue: 12, P. 1 - 9

Published: Jan. 19, 2025

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of cancer biology, yet their roles in breast cancer, particularly triple-negative (TNBC), remain incompletely understood. Through a custom siRNA library screen targeting TNBC-associated lncRNAs MDA-MB-231 and BT-549 TNBC cell models, we identified LURAP1L-AS1 key modulator progression. Survival analysis patients demonstrated significant association between elevated expression poor clinical outcomes. knockdown significantly impaired colony formation organoid growth associated with increased apoptosis thus highlighting its role promoting tumorigenicity. RNA sequencing LURAP1L-AS1-depleted cells revealed dysregulation pathways related to proliferation, apoptosis, migration, processing. Bioinformatics predicted function competitive endogenous (ceRNA), sponging microRNAs, such miR-7a-5p, miR-101-3p, miR-181a-5p, miR-27a-3p, thereby modulating oncogenes including EZH2, MCL1, KRAS, which linked survival, metastasis. In addition TNBC, correlation using patient datasets ESR1 expression, suggesting broader impact across subtypes. Concordantly, depletion inhibited estrogen receptor-positive (ER+) MCF7 organotypic growth. Our findings establish functional lncRNA that promotes progression, potential for use RNA-based therapies cancer.

Language: Английский

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