Mechanism of interaction between autophagy and apoptosis in cancer

APOPTOSIS, Journal Year: 2021, Volume and Issue: 26(9-10), P. 512 - 533

Published: Sept. 12, 2021

Language: Английский

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lncRNA SNHG11 Promotes Gastric Cancer Progression by Activating the Wnt/β-Catenin Pathway and Oncogenic Autophagy

Molecular Therapy, Journal Year: 2020, Volume and Issue: 29(3), P. 1258 - 1278

Published: Oct. 15, 2020

Long non-coding RNAs (lncRNAs) are under active investigation in the development of cancers, including gastric cancer (GC). Oncogenic autophagy is required for cell survival. The present study aimed to investigate regulatory role lncRNA small nucleolar host gene 11 (SNHG11) GC. We show that SNHG11 upregulated GC, and its upregulation correlated with dismal patient outcomes. Functionally, aggravated oncogenic facilitate proliferation, stemness, migration, invasion, epithelial-to-mesenchymal transition (EMT) Mechanistically, post-transcriptionally catenin beta 1 (CTNNB1) related 12 (ATG12) through miR-483-3p/miR-1276, while processing precursor (pre-)miR-483/pre-miR-1276 was hindered by SNHG11. induced GSK-3β ubiquitination interacting Cullin 4A (CUL4A) further activate Wnt/β-catenin pathway. Intriguingly, regulated a manner dependent on ATG12 rather than pathway, whereas contributed malignant behaviors GC cells via both pathways. Finally, shown be transcriptionally TCF7L2. In conclusion, we reveal an onco-lncRNA might promising prognostic therapeutic target

Language: Английский

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Targeting HNRNPU to overcome cisplatin resistance in bladder cancer

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 7, 2022

The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. genes that associated with cisplatin resistance remain unclear. Herein, we aimed identify BUC. EXPERIMENTAL DESIGN: cytotoxicity was evaluated six cancer cell lines compare their responses cisplatin. T24 cells exhibited lowest sensitivity therefore selected explore mechanisms We performed genome-wide CRISPR screening vitro, identified gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) top candidate related Epigenetic transcriptional profiles HNRNPU-depleted after treatment were analyzed investigate relationship between HNRNPU In vivo experiments also demonstrate function depletion sensitivity.Significant correlation found expression level lines. high expressing cells, knockout inhibited proliferation, invasion, migration. addition, loss promoted apoptosis S-phase arrest treated Data from Cancer Genome Atlas (TCGA) demonstrated significantly higher tumor tissues than normal tissues. High negatively correlated patient survival. Transcriptomic profiling analysis showed enhanced by regulating DNA damage repair genes. Furthermore, it regulates chemosensitivity affecting neurofibromin 1 (NF1).Our study is cells. Inhibition could be a potential therapy for cisplatin-resistant cancer.

Language: Английский

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Tumor-secreted exosomal miR-141 activates tumor-stroma interactions and controls premetastatic niche formation in ovarian cancer metastasis

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

Published: Jan. 9, 2023

Abstract Background Metastatic colonization is one of the critical steps in tumor metastasis. A pre-metastatic niche required for metastatic and determined by tumor-stroma interactions, yet mechanistic underpinnings remain incompletely understood. Methods PCR-based miRNome profiling, qPCR, immunofluorescent analyses evaluated expression exosomal miR-141 cell-to-cell communication. LC-MS/MS proteomic profiling Dual-Luciferase identified YAP1 as direct target miR-141. Human cytokine ChIP, luciferase reporter assays, subcellular fractionation confirmed modulating GROα production. series vitro tumorigenic an ex vivo model Yap1 stromal conditional knockout (cKO) mouse demonstrated roles miR-141/YAP1/GROα/CXCR1/2 signaling cascade. RNAi, CRISPR/Cas9 CRISPRi systems were used gene silencing. Blood sera, OvCa tissue samples, array included clinical correlations. Results Hsa-miR-141-3p (miR-141), miRNA, highly secreted ovarian cancer cells reprograms fibroblasts into proinflammatory cancer-associated (CAFs), facilitating colonization. study showed that targeted YAP1, a effector Hippo pathway, reducing nuclear YAP1/TAZ ratio enhancing production from fibroblasts. Stromal-specific murine models shaped GROα-enriched microenvironment, colonization, but this effect was reversed after Cxcr1/2 depletion cells. The YAP1/GROα correlation highlighting relevance research providing potential therapeutic intervention impeding premetastatic formation progression cancers. Conclusions This uncovers OvCa-derived microRNA mediating interactions tumor-promoting through activating YAP1/GROα/CXCRs cascade, new insight therapy patients with peritoneal metastases.

Language: Английский

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miRNA profile in ovarian cancer

Experimental and Molecular Pathology, Journal Year: 2020, Volume and Issue: 113, P. 104381 - 104381

Published: Jan. 16, 2020

Language: Английский

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Understanding the Role of the Transcription Factor Sp1 in Ovarian Cancer: from Theory to Practice

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(3), P. 1153 - 1153

Published: Feb. 9, 2020

Ovarian cancer (OC) is one of the deadliest cancers among women contributing to high risk mortality, mainly owing delayed detection. There no specific biomarker for its detection in early stages. However, recent findings show that over-expression specificity protein 1 (Sp1) involved many OC cases. The ubiquitous transcription Sp1 apparently mediates maintenance normal and cancerous biological processes such as cell growth, differentiation, angiogenesis, apoptosis, cellular reprogramming tumorigenesis. exerts effects on genes containing putative GC-rich Sp1-binding site their promoters. A better understanding mechanisms underlying factor (TF) regulation functions tumorigenesis could help identify novel prognostic markers, target stem cells (CSCs) by following enable development therapies future generations. In this review, we address structure, function, biology cells, underpinning involvement addition, have highlighted influence TF iPSCs how it plays a role controlling CSCs. This review highlights drugs targeting action cells. conclusion, predict research direction will be highly beneficial treatment, chemotherapeutic emerge promising therapy OC.

Language: Английский

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MiR-141–3p inhibits cell proliferation, migration and invasion by targeting TRAF5 in colorectal cancer

Biochemical and Biophysical Research Communications, Journal Year: 2019, Volume and Issue: 514(3), P. 699 - 705

Published: May 9, 2019

Emerging evidence has shown that abnormal microRNA (miRNA) expression play an important role in initiation, progression and metastasis several tumors, including colorectal cancer. Here, we attempted to explore the function of miR-141-3p MiR-141-3p was measured tissue samples, cancer cell lines normal human colon epithelium line FHC by real-time PCR. The biological roles were investigated both vitro a mouse model vivo. Bioinformatics analysis, PCR, Western blot luciferase reporter analysis performed validate association between its potential targets. Our results suggested down-regulated tissues compared cells. Patients with low had poor outcome. In addition, Overexpression significantly delayed proliferation, migration, invasion cells vitro, as well obviously attenuated tumor growth xenograft Furthermore, showed inhibited via directly targeting necrosis factor receptor-associated 5 (TRAF5). summary, acts suppressor, TRAF5 indicated might be therapeutic target for

Language: Английский

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Role of microRNAs as Clinical Cancer Biomarkers for Ovarian Cancer: A Short Overview

Cells, Journal Year: 2020, Volume and Issue: 9(1), P. 169 - 169

Published: Jan. 9, 2020

Ovarian cancer has the highest mortality rate among gynecological cancers. Early clinical signs are missing and there is an urgent need to establish early diagnosis biomarkers. MicroRNAs promising biomarkers in this respect. In paper, we review most recent advances regarding alterations of microRNAs ovarian cancer. We have briefly described contribution miRNAs mechanisms invasion, metastasis, chemotherapy sensitivity. also summarized underwent by solid tumors, animal models for cancer, various cell lines as compared previous reviews that were only focused circulating context, consider biomarker screening should not be limited per se, but rather simultaneous detection same microRNA alteration order understand differences between nucleic acids vs. late stages Moreover, vitro vivo validate these microRNAs, which could very helpful preclinical testing platforms pharmacological and/or molecular genetic approaches targeting microRNAs. The enormous quantity data produced studies role act synergistically tumorigenesis associated with subtypes, gathered, integrated, adequate methods, including clustering. respect, clustering analysis contribute discovery best biomarkers-based assays will enable rapid, efficient, cost-effective stages. conclusion, identifying appropriate might improve life quality patients.

Language: Английский

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Ovarian cancer: epigenetics, drug resistance, and progression

Cancer Cell International, Journal Year: 2021, Volume and Issue: 21(1)

Published: Aug. 17, 2021

Abstract Ovarian cancer (OC) is one of the most common malignant tumors in women. OC associated with activation oncogenes, inactivation tumor suppressor genes, and abnormal cell signaling pathways. Moreover, epigenetic processes have been found to play an important role tumorigenesis. Epigenetic do not change DNA sequences but regulate gene expression through methylation, histone modification, non-coding RNA. This review comprehensively considers importance epigenetics OC, a focus on microRNA long These types RNA are promising molecular markers therapeutic targets that may support precision medicine OC. methylation inhibitors deacetylase be useful for such targeting, possible novel approach combining these two therapies. Currently, clinical application approaches limited by multiple obstacles, including heterogeneity insufficient sample sizes reported studies, non-optimized methods detecting potential markers. Nonetheless, patient diagnosis, treatment, prognosis area future investigation.

Language: Английский

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The role of miRNAs in ovarian cancer pathogenesis and therapeutic resistance – A focus on signaling pathways interplay

Pathology - Research and Practice, Journal Year: 2022, Volume and Issue: 240, P. 154222 - 154222

Published: Nov. 15, 2022

Language: Английский

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