Background: Chemoresistance has become a major obstacle for cancer therapy in clinic. Long noncoding RNAs (lncRNAs) have been reported to play critical roles in the development of chemoresistance in various tumors, including gastric cancer (GC). However, the role of HOXA transcript at the distal tip (HOTTIP) within extracellular vesicles (exosomes) in cisplatin-resistant GC cells remains largely unknown.
Materials And Methods: Cell proliferation, migration and invasion were detected using Cell Counting Kit-8 (CCK-8) and transwell assays, respectively. Western blot assay was employed to analyze the protein levels of E-cadherin, N-cadherin, Vimentin, CD63, CD83, GRP78, HMGA1, and high-mobility group A1 (HMGA1). The expression levels of HOTTIP, microRNA-218 (miR-218) and HMGA1were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-218 and HOTTIP or HMGA1 was predicted by bioinformatics software and confirmed by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.
Results: Cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were promoted in cisplatin-resistant GC cells. HOTTIP level was upregulated in cisplatin-resistant GC cells and its downregulation enhanced cisplatin sensitivity. Moreover, extracellular HOTTIP could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating cisplatin resistance. Additionally, exosomal HOTTIP promoted cisplatin resistance via activating HMGA1 in GC cells. Interestingly, HMGA1 was a target of miR-218 and miR-218 could directly bind to HOTTIP. Clinically, high expression of exosomal HOTTIP in serum was associated with poor response to cisplatin treatment in GC patients.
Conclusion: Exosomal HOTTIP contributed to cisplatin resistance in GC cells by regulating miR-218/HMGA1 axis, providing a novel avenue for the treatment of GC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930390 | PMC |
| http://dx.doi.org/10.2147/OTT.S231846 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Morphine-Induced Elevation of Reactive Oxygen Species Attenuates Chemotherapy Efficacy in Diverse Cancer Cell Types.
Curr Mol Med
January 2025
Department of Anesthesiology, Baoan Central Hospital of Shenzhen, Shenzhen, Guangdong Province, China.
Background: Morphine, a mu-opioid receptor (MOR) agonist commonly utilized in clinical settings alongside chemotherapy to manage chronic pain in cancer patients, has exhibited contradictory effects on cancer, displaying specificity toward certain cancer types and doses.
Objective: The aim of this study was to conduct a systematic assessment and comparison of the impacts of morphine on three distinct cancer models in a preclinical setting.
Methods: Viability and apoptosis assays were conducted on a panel of cancer cell lines following treatment with morphine, chemotherapy drugs alone, or their combination.
Leptin increases chemosensitivity by inhibiting in colorectal cancer cells.
J Gastrointest Oncol
December 2024
Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou, China.
Background: Chemoresistance is a major cause of treatment failure in advanced colorectal cancer (CRC), severely impacting patient survival and quality of life. While conventional chemotherapy regimens can somewhat control tumor progression, their effectiveness is frequently compromised by the development of drug resistance in cancer cells. The aim of this study is to verify and elucidate the specific mechanisms by which leptin enhances chemosensitivity in CRC, providing valuable insights for the development of new combination chemotherapy options.
View Article and Find Full Text PDFUSP1 promotes pancreatic cancer progression and autophagy by deubiquitinating ATG14.
J Biol Chem
January 2025
Institute of Immunopharmaceutical Sciences, NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, Guangxi, China. Electronic address:
Pancreatic ductal adenocarcinoma (PDAC) is characterized by extremely poor prognosis, high mortality and limited therapeutic strategy. Autophagy is hyperactivated in PDAC and targeting autophagy are emerging as promising therapeutic strategies. The dysfunction of deubiquitinase USP1 results in tumorigenesis and chemotherapy resistance.
View Article and Find Full Text PDFEngineered biomimetic cisplatin-polyphenol nanocomplex for chemo-immunotherapy of glioblastoma by inducing pyroptosis.
J Nanobiotechnology
January 2025
Department of Pharmacy The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
Glioblastoma multiforme (GBM) is characterized by pronounced immune escape and resistance to chemotherapy-induced apoptosis. Preliminary investigations revealed a marked overexpression of gasdermin E (GSDME) in GBM. Notably, cisplatin (CDDP) demonstrated a capacity of inducing pyroptosis by activating caspase-3 to cleave GSDME, coupled with the release of proinflammatory factors, indicating the potential as a viable approach of inducing anti-tumor immune activation.
View Article and Find Full Text PDFDNAJC15 is a mitochondrial TIMM23-related co-chaperonin known for its role in regulating oxidative phosphorylation efficiency, oxidative stress response and lipid metabolism. Recently, it has been proposed that the loss of DNAJC15 correlates with cisplatin (CDDP)-resistance onset in ovarian cancer (OC), suggesting this protein as a potential prognostic factor during OC progression. However, the molecular mechanisms through which DNAJC15 contributes to CDDP response remains poorly investigated.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!