Background: The acquisition of drug resistance has been considered as a main obstacle for cancer chemotherapy. Tumor protein 53 target gene 1 (TP53TG1), a p53-induced lncRNA, plays a vital role in the progression of human cancers. However, little is known about the detailed function and molecular mechanism of TP53TG1 in cisplatin resistance of NSCLC.
Methods: qRT-PCR analysis was used to detect the expression of TP53TG1, miR-18a and PTEN mRNA in NSCLC tissues and cells. Western blot analysis was performed to determine the protein level of PTEN and cleaved caspase-3. Cell viability and IC50 value were measured by MTT assay. Cell apoptosis was confirmed by flow cytometry assay. Subcellular fractionation assay was used to identify the subcellular location of TP53TG1. Dual-luciferase reporter assay, RNA pull down assay and RNA immunoprecipitation assay were carried out to verify the interaction between TP53TG1 and miR-18a. Xenografts in nude mice were established to verify the effect of TP53TG1 on cisplatin sensitivity of NSCLC cells in vivo.
Results: TP53TG1 level was downregulated in NSCLC tissues and cell lines. Upregulated TP53TG1 enhanced cisplatin sensitivity and apoptosis of A549/DDP cells, while TP53TG1 depletion inhibited cisplatin sensitivity and apoptosis of A549 cells. TP53TG1 suppressed miR-18a expression in A549 cells. Moreover, TP53TG1-mediated enhancement effect on cisplatin sensitivity was abated following the restoration of miR-18a expression in A549/DDP cells, while si-TP53TG1-induced decrease of cisplatin sensitivity and apoptosis was counteracted by miR-18a inhibitor in A549 cells. Furthermore, TP53TG1 promoted PTEN expression via inhibiting miR-18a. Finally, TP53TG1 sensitized NSCLC cells to cisplatin in vivo.
Conclusion: TP53TG1 increased the sensitivity of NSCLC cells to cisplatin by modulating miR-18a/PTEN axis, elucidating a novel approach to boost the effectiveness of chemotherapy for NSCLC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863826 | PMC |
| http://dx.doi.org/10.1186/s13578-018-0221-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Knockdown of miR-182 changes the sensitivity of triple-negative breast cancer cells to cisplatin.
Nucleosides Nucleotides Nucleic Acids
January 2025
Division of Hematology, Department of Internal Medicine, Medical Faculty, Tekirdağ Namık Kemal University, Tekirdağ, Turkey.
Breast cancer is the most common malignancy that affects women. MicroRNAs (miRNAs) play an essential role in cancer therapy and regulate many biological processes such as cisplatin resistance. The study's objective was to determine whether miR-182 dysregulation was the cause of cisplatin resistance in TNBC cell line MDA-MB-231.
View Article and Find Full Text PDFDoxycycline Restores Gemcitabine Sensitivity in Preclinical Models of Multidrug-Resistant Intrahepatic Cholangiocarcinoma.
Cancers (Basel)
January 2025
Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
Background/objectives: Intrahepatic cholangiocarcinoma (iCCA) is a malignant liver tumor with a rising global incidence and poor prognosis, largely due to late-stage diagnosis and limited effective treatment options. Standard chemotherapy regimens, including cisplatin and gemcitabine, often fail because of the development of multidrug resistance (MDR), leaving patients with few alternative therapies. Doxycycline, a tetracycline antibiotic, has demonstrated antitumor effects across various cancers, influencing cancer cell viability, apoptosis, and stemness.
View Article and Find Full Text PDFSynergistic Effects of Mistletoe Lectin and Cisplatin on Triple-Negative Breast Cancer Cells: Insights from 2D and 3D In Vitro Models.
Int J Mol Sci
January 2025
College of Pharmacy, Sunchon National University, Suncheon 57922, Republic of Korea.
Triple-negative breast cancer (TNBC) remains a challenging subtype due to its aggressive nature and limited treatment options. This study investigated the potential synergistic effects of Korean mistletoe lectin ( L. agglutinin, VCA) and cisplatin on MDA-MB-231 TNBC cells using both 2D and 3D culture models.
View Article and Find Full Text PDFSRC enhanced cisplatin resistance in bladder cancer by reprogramming glycolysis and pentose phosphate pathway.
Commun Biol
January 2025
Institute of Urology, The Second Hospital of Lanzhou University, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou, Gansu, China.
The development of cisplatin resistance often results in a grim prognosis in advanced or recurrent bladder cancer. However, effective treatment strategies for cisplatin resistance have not been well established. Herein, we found that overactivation of SRC is associated with cisplatin-resistance.
View Article and Find Full Text PDFTargeting on the PI3K/mTOR: a potential treatment strategy for clear cell ovarian carcinoma.
Cancer Chemother Pharmacol
January 2025
Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.
Purpose: Ovarian clear cell carcinoma is a highly malignant gynecological tumor characterized by a high rate of chemotherapy resistance and poor prognosis. The PI3K/AKT/mTOR pathway is well-known to be closely related to the progression of various malignancies, and recent studies have indicated that this pathway may play a critical role in the progression and worsening of OCCC.
Methods: In this study, we investigated the combined effects of WX390, a dual inhibitor of PI3K/mTOR, and cisplatin on OCCC through both in vitro and in vivo experiments to further elucidate their therapeutic effects.
Want 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!