Abstract

Adenocarcinoma is one of the most common pathological types of human lung cancer and has the highest incidence and mortality rates worldwide. Resistance to paclitaxel (PTX), the standard chemotherapy agent for treatment of lung adenocarcinoma, is a major clinical obstacle. Sensitive markers are urgently required for the diagnosis and characterization of lung cancer, as well as to manage drug resistance. Previous studies have described the activity of long non-coding RNAs (lncRNAs) in human lung cancer and chemotherapy resistance. In previous studies, lncRNA ENST00000500843 was identified to be downregulated in PTX-resistant A549 human lung cancer cells. However, the roles of this lncRNA in the development of lung adenocarcinoma and its mechanism in PTX resistance, to the best of our knowledge, have not been described. In the present study, 56 pairs of lung adenocarcinoma and normal adjacent tissue samples were collected. Reverse transcription-quantitative PCR revealed that the expression levels of lncRNA ENST00000500843 were lower in lung adenocarcinoma tissues and PTX-resistant A549 cells when compared with normal adjacent tissues and A549 cells. Decreased expression levels of lncRNA ENST00000500843 in lung adenocarcinoma tissues were associated with tumor diameter, the degree of pathological differentiation and metastasis of lymph nodes. Additionally, patients with low expression levels of ENST00000500843 exhibited poorer overall survival and progression-free survival rates. Furthermore, the present study demonstrated that knockdown of lncRNA ENST00000500843 with small interfering RNA decreased the likelihood of apoptosis in A549 cells and promoted resistance to PTX. This indicated that lncRNA ENST00000500843 may be a useful diagnostic marker of lung cancer and a good prognostic marker for resistance to treatment with PTX.

Highlights

  • Lung cancer is one of the leading causes of cancer‐associated mortality worldwide, and its incidence, along with aging populations and environmental pollution, is increasing [1]

  • The present study investigated the role of long non‐coding RNAs (lncRNAs) ENST00000500843 in the development of lung adenocarcinoma and its clinical relevance, as well as its effect on PTX resistance

  • The present study demonstrated that the expression levels of lncRNA ENST00000500843 were significantly downregulated in lung adenocarcinoma tissues and A549/PTX cells compared with normal adjacent tissues and A549 cells

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Summary

Introduction

Lung cancer is one of the leading causes of cancer‐associated mortality worldwide, and its incidence, along with aging populations and environmental pollution, is increasing [1]. This is leading to a large social and economic burden, which seriously affects the development of health systems and the economy around the world [2]. The mechanism behind PTX resistance is multifactorial and complex, and presents a significant challenge in the successful treatment of lung cancer [9]. An improved understanding of the molecular mechanism underlying the development of this form of resistance is required. The identification of molecular markers associated with PTX‐associated tumor response could help to select patients who are likely to benefit from chemotherapy [10]

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