LncRNA ADAMTS9-AS2 inhibits gastric cancer (GC) development and sensitizes chemoresistant GC cells to cisplatin by regulating miR-223-3p/NLRP3 axis

Aging, Год журнала: 2020, Номер 12(11), С. 11025 - 11041

Опубликована: Июнь 9, 2020

The role of LncRNA ADAMTS9-AS2 in the regulation chemoresistance gastric cancer (GC) is largely unknown. Here we found that was low-expressed GC tissues and cells compared to their normal counterparts. In addition, inhibited miR-223-3p expressions by acting as competing endogenous RNA, levels showed negative correlations tissues. Of note, overexpression cell viability motility sponging miR-223-3p. were lower, higher cisplatin-resistant (CR-GC) than parental cisplatin-sensitive (CS-GC) cells. enhanced cytotoxic effects cisplatin on CR-GC cells, which reversed overexpressing Furthermore, increased NLRP3 targeting miR-223-3p, upregulation triggered pyroptotic death treated activating inflammasome through downregulating Finally, promoting abrogated pyroptosis inhibitor Necrosulfonamide (NSA). Collectively, acted a tumor suppressor sensitivity mediated

Язык: Английский

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Novel Function of lncRNA ADAMTS9-AS2 in Promoting Temozolomide Resistance in Glioblastoma via Upregulating the FUS/MDM2 Ubiquitination Axis

Frontiers in Cell and Developmental Biology, Год журнала: 2019, Номер 7

Опубликована: Окт. 2, 2019

Background: LncRNAs have been shown to play essential roles in cancer therapeutic response. However, the detailed mechanism of lncRNAs temozolomide (TMZ) resistance glioblastoma (GBM) remain be elucidated. Methods: To elucidate maintaining TMZ resistance, we constructed two TMZ-resistant GBM cell lines (T98G-R/U118-R). from four public datasets were reanalyzed, and candidate lncRNA ADAMTS9-AS2 was evaluated TMZ-treated patients vitro lines. Results: Reanalysis expression profiles identified as significantly overexpressed cells positively associated with IC50 cells. Overexpression also poor response shorter progression-free survival (PFS) patients. Knockdown inhibited proliferation attenuated TMZ, well mitigating invasion migration Subsequent investigations indicated that reduced suppressed FUS protein, which predicted a direct substrate ADAMTS9-AS2. Expression trends directly correlated those ADAMTS9-AS2, by increasing concentrations prolonged treatment TMZ. RNA pull-down RIP assays both endogenous exogenous binds RRM Znf_RanBP2 domains FUS, consequently protein expression. half-life decreased stability via K48 ubiquitin degradation. Moreover, E3 ubiquitin-protein ligase MDM2 interacts down regulates while facilitate its binding MDM2. interaction between mediates ubiquitination. Additionally, knockdown ADAMTS9-AS2/FUS signaling axis alleviated progression metastasis Conclusion: possessed novel function promotes upregulating FUS/MDM2 The or combination competitively inhibiting MDM2-dependent ubiquitination resulting enhanced resistance. Our results suggest ADAMTS9-AS2/ may represent suitable prognostic biomarker potential target therapy.

Язык: Английский

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Exosomes secreted by M2 macrophages promote cancer stemness of hepatocellular carcinoma via the miR-27a-3p/TXNIP pathways

International Immunopharmacology, Год журнала: 2021, Номер 101, С. 107585 - 107585

Опубликована: Сен. 30, 2021

Язык: Английский

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A review on the role of long non-coding RNA and microRNA network in clear cell renal cell carcinoma and its tumor microenvironment

Cancer Cell International, Год журнала: 2023, Номер 23(1)

Опубликована: Фев. 2, 2023

Renal cell carcinoma (RCC) is the second lethal urogenital malignancy with increasing incidence and mortality in world. Clear renal (ccRCC) one major subtype of RCC, which accounts for about 70 to 80% all RCC cases. Although many innovative therapeutic options have emerged during last few decades, efficacy these treatments ccRCC patients very limited. To date, prognosis advanced or metastatic still poor. The 5-year survival rate remains less than 10%, mainly attributes complexity heterogeneity tumor microenvironment (TME). It has been demonstrated that long non-coding RNAs (lncRNAs) perform an indispensable role initiation progression various tumors. They mostly function as sponges microRNAs (miRNAs) regulate expression target genes, finally influence growth, metastasis, apoptosis, drug resistance TME cells. However, lncRNA/miRNA/mRNA axis poorly understood. In this review, we summarized biological pathogenesis ccRCC, then discussed how TME, highlighted their potential application novel biomarkers targets ccRCC.

Язык: Английский

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Long Non-Coding RNA Profile Study Identifies an Immune-Related lncRNA Prognostic Signature for Kidney Renal Clear Cell Carcinoma

Frontiers in Oncology, Год журнала: 2020, Номер 10

Опубликована: Авг. 20, 2020

Kidney renal clear cell carcinoma (KIRC) is the predominant pathological subtype of (RCC) in adults. Long non-coding RNAs (lncRNAs) are an important class gene expression regulators and serve fundamental roles immune regulation. The intent this study to develop a novel immune-related lncRNA signature accurately predict prognosis for KIRC patients. Here, we performed genome-wide comparative analysis profiles 537 patients from Cancer Genome Atlas (TCGA) database. Cox regression model-identified lncRNAs were extracted constructing five (AC008105.3, LINC02084, AC243960.1, AC093278.2, AC108449.2) with ability Univariate multivariate analyses demonstrated that could act as independent prognostic predictor overall survival (OS). With further investigation on different clinicopathological parameters, found divide samples into high-risk groups shorter OS low-risk longer subgroups. Principal component suggested drew distinction between high- based lncRNAs. status two was observed set enrichment ESTIMATE algorithm. Except expressions other four significantly upregulated tumor tissues. In summary, identified immune-lncRNA had clinical implications prediction be exploited underlying therapeutic targets

Язык: Английский

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Long non-coding RNA (lncRNA) PVT1 in drug resistance of cancers; focus on pathological mechanisms

Pathology - Research and Practice, Год журнала: 2024, Номер unknown, С. 155119 - 155119

Опубликована: Янв. 1, 2024

Язык: Английский

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DARS-AS1 promotes clear cell renal cell carcinoma by sequestering miR-194-5p to up-regulate DARS

Biomedicine & Pharmacotherapy, Год журнала: 2020, Номер 128, С. 110323 - 110323

Опубликована: Июнь 8, 2020

Clear cell renal carcinoma (ccRCC), the most frequent subtype of (RCC), is characterized by high relapse rate and mortality. Long non-coding RNAs (lncRNAs) are critical participants during cancer development. LncRNA DARS antisense RNA 1 (DARS-AS1), a newly-found lncRNA, not specifically reported in ccRCC. However, Gene Expression Profiling Interactive Analysis (GEPIA) starBase databases revealed up-regulation DARS-AS1 Current study investigated function mechanism Functional assays including colony formation assay, EdU caspase-3 activity detection, flow cytometry analysis JC-1 assay were implemented to identify role As result, silencing retarded proliferation facilitated apoptosis ccRCC cells. Moreover, mainly cytoplasmic localization lncRNA was verified Then, we demonstrated that positively regulated its nearby gene, aspartyl-tRNA synthetase (DARS), sequestering miR-194−5p. testified as oncogene worked tumor-facilitator through miR-194−5p/DARS signaling. In summary, this firstly uncovered boosted expression via absorbing miR-194−5p, therefore contributing malignancy Our findings may be helpful for opening new strategies treatment.

Язык: Английский

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lncRNA and Mechanisms of Drug Resistance in Cancers of the Genitourinary System

Cancers, Год журнала: 2020, Номер 12(8), С. 2148 - 2148

Опубликована: Авг. 3, 2020

Available systemic treatment options for cancers of the genitourinary system have experienced great progress in last decade. However, a large proportion patients eventually develop resistance to treatment, resulting disease progression and shorter overall survival. Biomarkers indicating increasing cancer therapies are yet enter clinical routine. Long non-coding RNAs (lncRNA) non-protein coding RNA transcripts longer than 200 nucleotides that exert multiple types regulatory functions all known cellular processes. Increasing evidence supports role lncRNAs development progression. Additionally, their involvement drug across various entities, including malignancies, starting be discovered. Consequently, been suggested as factors novel therapeutic strategies overcome cancer. In this review, existing evidences on mechanisms system, renal cell carcinoma, bladder cancer, prostate testicular will highlighted discussed facilitate encourage further research field. We summarize significant number with proposed pathways available reported studies.

Язык: Английский

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Identification of a 14-lncRNA Signature and Construction of a Prognostic Nomogram Predicting Overall Survival of Gastric Cancer

DNA and Cell Biology, Год журнала: 2020, Номер 39(9), С. 1532 - 1544

Опубликована: Июль 9, 2020

Increasing evidence suggests that aberrant long noncoding (lnc) RNA expression plays a vital role in gastric cancer (GC) initiation and progression. Thus, we aimed to develop lncRNA-based risk signature nomogram predict overall survival (OS) for patients with GC. Our primary cohort was composed of 341 clinical lncRNA data The Cancer Genome Atlas stomach adenocarcinoma (TCGA STAD), the internal validation 172 randomly assigned patients, external 300 from GSE62254 dataset. A were developed validated on cohorts. Furthermore, gene set enrichment analysis (GSEA) used investigate pathway signature. patterns several lncRNAs also investigated samples 10 GC patients. We identified 14-lncRNA highly associated OS GC, which performed well evaluation C-index, area under curve, calibration curves. In addition, univariate multivariate Cox regression analyses indicated an independent predictive factor Therefore, incorporating factors constructed suggested powerful values TCGA other two GSEA may regulate autophagy pathway, affecting tumorigenesis prognosis Experimental demonstrated showed same trend both our STAD These results suggest effective prognostic indicators

Язык: Английский

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LncRNAs in the Regulation of Genes and Signaling Pathways through miRNA-Mediated and Other Mechanisms in Clear Cell Renal Cell Carcinoma

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(20), С. 11193 - 11193

Опубликована: Окт. 17, 2021

The fundamental novelty in the pathogenesis of renal cell carcinoma (RCC) was discovered as a result recent identification role long non-coding RNAs (lncRNAs). Here, we discuss several mechanisms for dysregulation expression protein-coding genes initiated by lncRNAs most common and aggressive type kidney cancer—clear RCC (ccRCC). A model competitive endogenous RNA (ceRNA) is considered, which lncRNA acts on through lncRNA/miRNA/mRNA axis. For studied oncogenic lncRNAs, such HOTAIR, MALAT1, TUG1, regulatory axes were identified ccRCC, demonstrating number sites various miRNAs. Interestingly, LINC00973/miR-7109/Siglec-15 axis represents novel agent that can suppress immune response patients with serving valuable target addition to PD1/PD-L1 pathway. Other action involving direct binding proteins, mRNAs, genes/DNA, are also considered. Our review briefly highlights methods verified. We pay special attention protein targets signaling pathways associated ccRCC. Thus, these new data different functioning provide basis understanding ccRCC prognostic markers therapy.

Язык: Английский

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