Therapeutic Potential of lncRNA-PVT۱ Silencing in Enhancing Chemosensitivity and Reducing Lung Cancer Tumorigenicity

Lung cancer remains a worrisome malignancy with considerable morbidity and mortality. Recent studies have shown that long non-coding RNAs (lncRNAs) are dysregulated in lung cancer, and this dysregulation substantially contributes to lung cancer tumorigenesis. The current study investigated the significance of lncRNA-PVT۱ in tumorigenesis and docetaxel resistance of A۵۴۹ cells using in vitro assays. The MTT, annexin V/PI staining, cell cycle, and scratch assays were conducted to study the effect of lncRNA-PVT۱ silencing on the cell viability, chemosensitivity, apoptosis, cell cycle, and migration of A۵۴۹ cells. The expression levels of MMP۲, CASP۳, c-Myc, and BCL۲ were investigated to study the molecular mechanisms of lncRNA-PVT۱ silencing. LncRNA-PVT۱ silencing decreases the cell viability and migration of A۵۴۹ cells. Also, lncRNA-PVT۱-siRNA improves the apoptosis rate and arrests the cell cycle at the sub-G۱ phase. In addition, lncRNA-PVT۱ silencing downregulates MMP۲, c-Myc, and BCL۲ expression and upregulates CASP۳ expression. In addition, lncRNA-PVT۱ silencing improves the anti-tumoral potential of docetaxel on A۵۴۹ cells. The results of this in vitro study indicate that the combined treatment of lncRNA-PVT۱ silencing with docetaxel might be considered a therapeutic option for non-small cell lung cancer.Lung cancer is the leading cause of cancer-attributable death and the second most common malignancy in ۲۰۲۴ in the United States (۱). Classically, lung cancers are divided into two groups, i.e., non-small cell carcinoma and small cell carcinoma, with non-small lung cancer being responsible for ۸۰% of the cases. Long non-coding RNAs (lncRNAs) are a class of transcripts that are longer than ۲۰۰ nucleotides; these non-coding RNAs have considerable roles in gene regulation at the epigenetic, transcriptional, and post-transcriptional levels. LncRNAs can act as sponges for microRNAs, interact with histone-modifier enzymes and transcriptional factors to modify gene regulation, and serve as anti-sense for messenger RNAs (mRNAs). Also, lncRNAs are the pivotal part of the competing endogenous RNA networks that have remarkable roles in regulating noticeable numbers of genes. Therefore, lncRNAs can govern different cell signaling pathways and cell behavior (۲). In this respect, growing evidence indicates the importance of dysregulated lncRNAs in lung cancer tumorigenesis and chemoresistance. LncRNA-PVT۱ is an oncogenic lncRNA that is upregulated in various malignancies, and its upregulation is generally associated with a poor prognosis for affected patients (۳). Herein, we studied the significance of lncRNA-PVT۱ in the apoptosis, cell viability, migration, cell cycle, and gene expression of lung non-small cell lung cancer and the therapeutic potentiality of the combined treatment of docetaxel with lncRNA-PVT۱ silencing on non-small cell lung cancer using in vitro assays.

کلیدواژه ها:

Lung cancer ، lncRNA-PVT۱ ، Docetaxel Apoptosis ، Metastasis ، Chemoresistance