LncRNA LINC01134 Contributes to Radioresistance in Hepatocellular Carcinoma by Regulating DNA Damage Response via MAPK Signaling Pathway

Frontiers in Pharmacology, Год журнала: 2022, Номер 12

Опубликована: Янв. 31, 2022

Hepatocellular carcinoma (HCC) is a highly mortal cancer that could be treated by radiotherapy. DNA damage response (DDR) vital factor affecting development after Long non-coding RNAs (lncRNAs) have been revealed to regulate and repair in cells. Nevertheless, the function of long intergenic non-protein coding RNA 1134 (LINC01134) has not explored DDR. In this study, we targeted digging into LINC01134 DDR exploring underlying mechanism HCC RT-qPCR was employed measure expression, found significantly upregulated Functional analysis suggested depletion attenuated radioresistance cells facilitating damage. vivo assays demonstrated hindered tumor growth. Mechanism unveiled sequestered microRNA-342-3p (miR-342-3p) recruited insulin-like growth 2 mRNA binding protein (IGF2BP2) modulate mitogen-activated kinase 1 (MAPK1) consequently activating MAPK signaling pathway. Rescue validated LINC01134/miR-342-3p/MAPK1 axis radio-resistant conclusion, might identified useful biomarker for therapy HCC.

Язык: Английский

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Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Апрель 28, 2022

Hepatocellular carcinoma (HCC) is a common malignancy with higher mortality, and means are urgently needed to improve the prognosis. T cell exclusion (TCE) plays pivotal role in immune evasion, lncRNAs represent large group of tumor development progression modulators. Using TCGA HCC dataset (n=374), we identified 2752 differentially expressed 702 TCE-associated lncRNAs, which 336 were both groups. As using univariate Cox regression analysis, those associated overall survival (OS) subjected LASSO-COX analysis develop prognosis signature. The model, consisted 11 was named 11LNCPS for 11-lncRNA signature, validated performed better than two previous models. In addition OS TCE, scores had significant correlation reduced infiltrations CD8+ cells dendritic (DCs) decreased Th1, Th2, pro B cells. expected, these infiltration alterations significantly worse HCC. Analysis published data indicates that HCCs transcriptomically similar responded PDL1 inhibitor. Of LINC01134 AC116025.2 seem more crucial, as their upregulations affected types’ OS, compromised responses LncRNAs impacted many cancer-associated biological processes signaling pathways, particularly involved function metabolism. should be useful predicting

Язык: Английский

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Lysine-Specific Demethylase 1 Promises to Be a Novel Target in Cancer Drug Resistance: Therapeutic Implications

Journal of Medicinal Chemistry, Год журнала: 2023, Номер 66(7), С. 4275 - 4293

Опубликована: Апрель 4, 2023

Chemotherapy, targeted therapy, and immunotherapy are effective against most tumors, but drug resistance remains a barrier to successful treatment. Lysine-specific demethylase 1 (LSD1), member of histone demethylation modifications, can regulate invasion, metastasis, apoptosis, immune escape tumor cells, which associated with tumorigenesis progression. Recent studies suggest that LSD1 ablation regulates resensitivity cells anticarcinogens containing checkpoint inhibitors (ICIs) via multiple upstream downstream pathways. In this review, we describe the recent findings about biology its role in development progression cancer resistance. Further, summarize have reversal or resensitive effect on discuss possibility targeting combination other agents surmount

Язык: Английский

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Solamargine enhanced gefitinib antitumor effect via regulating MALAT1/miR-141-3p/Sp1/IGFBP1 signaling pathway in non-small cell lung cancer

Carcinogenesis, Год журнала: 2023, Номер 44(6), С. 497 - 510

Опубликована: Май 5, 2023

Abstract Lung cancer is the leading cause of cancer-related deaths worldwide. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) showed great therapeutic efficacy for non-small cell lung (NSCLC) patients. However, acquired resistance severely limits clinical application and EGFR-TKIs. In current study, we found that solamargine (SM), a natural alkaloid derived from fruit Lycium tomato lobelia, has been to inhibit progression NSCLC enhance anticancer effect brief, SM significantly inhibited viability cells enhanced gefitinib (GFTN) erlotinib (ERL). Mechanistically, decreased expression MALAT1 induced miR-141-3p, whereas reduced SP1 protein levels. Interestingly, both Sp1 have classical conservative binding sites miR-141-3p in their 3ʹ-UTR regions. Silence overexpression Sp1. Subsequently, promoter activity IGFBP1 were upregulated by SM, which was not observed with overexpression. Moreover, inhibitory on blocked knockdown expression. More importantly, combination GFTN synergistically cancer. Similar results experiments vivo. Finally, relevance MALAT1, further validated using bioinformatics analysis. Taken together, confirmed EGFR-TKIs regulating MALAT1/miR-141-3p/Sp1/IGFBP1 signaling pathway. This study unravels novel mechanism suggests new potential NSCLC-associated therapy.

Язык: Английский

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FTO-mediated LINC01134 stabilization to promote chemoresistance through miR-140-3p/WNT5A/WNT pathway in PDAC

Cell Death and Disease, Год журнала: 2023, Номер 14(11)

Опубликована: Ноя. 1, 2023

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer most frequently detected at an advanced stage that limits treatment options to systemic chemotherapy, which has provided only marginal positive clinical outcomes. Currently, the first-line chemotherapeutic agent for PDAC gemcitabine (GEM). However, chemotherapy resistance GEM often overlooked in of due lack effective biological markers. Therefore, it crucial find new prognostic markers and therapeutic targets patients with PDAC. In this study, we identified novel regulatory mechanism development Here, report LINC01134 was significantly upregulated primary tumors from patients. vitro vivo functional studies revealed promotes through facilitating stem cell features modulating cycle. Mechanistically, interactes tumor suppressor miR-497-5p cells. Increased downregulates miR-140-3p oncogenic WNT5A expression. Moreover, m 6 A demethylase FTO participated upregulation by maintaining mRNA stability YTHDF2. Taken together, present study suggested FTO-mediated stabilization promote miR-140-3p/WNT5A/WNT pathway Our

Язык: Английский

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