The Role of miR-۱۴۲ and miR-۱۹۵ in Regulating Apoptotic Pathways in Non-Small Cell Lung Cancer

Lung cancer remains the leading cause of cancer-related mortality worldwide. non-small cell lung cancer (NSCLC) accounts for the majority of cases, despite advancements in treatment modalities, including chemotherapy, targeted therapy, and immunotherapy. The prognosis for NSCLC patients remains poor, largely due to challenges such as drug resistance and relapse. This study investigates the role of microRNAs (miRNAs) in the apoptotic pathways associated with NSCLC, focusing specifically on miR-۱۴۲ and miR-۱۹۵. These miRNAs have been implicated in regulating critical cellular processes, including proliferation and apoptosis.This study employed ۵-fluorouracil (۵-FU), a common chemotherapeutic agent, to assess its cytotoxic effects on the A۵۴۹ NSCLC cell line. The half-maximal inhibitory concentration (IC۵۰) for ۵-FU was determined to be ۱۰.۸۴ µg/mL after ۴۸ hours. Morphological studies revealed significant changes in cell structure post-treatment, while flow cytometry indicated that ۳۱.۳% of cells underwent early apoptosis. Quantitative real-time PCR (qRT-PCR) analyses demonstrated a significant upregulation of p۵۳ and Bax, alongside a downregulation of Bcl-۲ in treated cells, suggesting a shift towards pro-apoptotic signaling. Notably, miR-۱۴۲ expression was significantly increased, while miR-۱۹۵ showed a non-significant upward trend.These findings underscore the potential of miRNAs as therapeutic targets in NSCLC, particularly in overcoming drug resistance by modulating apoptotic pathways. Further exploration of miRNA-based therapies may yield innovative strategies to enhance treatment efficacy and improve patient outcomes in lung cancer.Lung cancer remains the leading cause of cancer-related mortality worldwide. non-small cell lung cancer (NSCLC) accounts for the majority of cases, despite advancements in treatment modalities, including chemotherapy, targeted therapy, and immunotherapy. The prognosis for NSCLC patients remains poor, largely due to challenges such as drug resistance and relapse. This study investigates the role of microRNAs (miRNAs) in the apoptotic pathways associated with NSCLC, focusing specifically on miR-۱۴۲ and miR-۱۹۵. These miRNAs have been implicated in regulating critical cellular processes, including proliferation and apoptosis. This study employed ۵-fluorouracil (۵-FU), a common chemotherapeutic agent, to assess its cytotoxic effects on the A۵۴۹ NSCLC cell line. The half-maximal inhibitory concentration (IC۵۰) for ۵-FU was determined to be ۱۰.۸۴ µg/mL after ۴۸ hours. Morphological studies revealed significant changes in cell structure post-treatment, while flow cytometry indicated that ۳۱.۳% of cells underwent early apoptosis. Quantitative real-time PCR (qRT-PCR) analyses demonstrated a significant upregulation of p۵۳ and Bax, alongside a downregulation of Bcl-۲ in treated cells, suggesting a shift towards pro-apoptotic signaling. Notably, miR-۱۴۲ expression was significantly increased, while miR-۱۹۵ showed a non-significant upward trend. These findings underscore the potential of miRNAs as therapeutic targets in NSCLC, particularly in overcoming drug resistance by modulating apoptotic pathways. Further exploration of miRNA-based therapies may yield innovative strategies to enhance treatment efficacy and improve patient outcomes in lung cancer.

کلیدواژه ها:

Apoptotic Pathways ، Lung Cancer ، miR-۱۴۲ ، miR-۱۹۵