Abstract
miRNA-21 is a single-stranded non-coding RNA that is highly expressed in a variety of tumor cells. It participates in tumor cell proliferation, metabolism, metastasis, and drug resistance. Here, we tested the potential mechanism of miRNA-21 in cisplatin-resistant non-small cell lung cancer A549/DDP (human lung adenocarcinoma drug-resistant cell line) cells. A549 and A549/DDP RNAs were sequenced to show that miRNA-21 was highly expressed in the latter, and this was verified by qRT-PCR. In addition, we found that miRNA-21 combined with cisplatin can significantly inhibit glycolysis and glycolysis rate-limiting enzyme protein expression in A549/DDP cells. We also found that miRNA-21 combined with cisplatin can promote A549/DDP cell death. Further investigations showed that miRNA-21 combined with cisplatin caused excessive inactivation of the pI3K/AKT/mTOR/HIF-1α signaling pathway in cisplatin-resistant A549/DDP cells. Hence, reduction of the expression of miRNA-21 in combination with cisplatin chemotherapy may effectively improve the therapeutic effect on patients with non-small cell lung cancer, and this may provide a theoretical basis for the treatment of this disease.
Highlights
Great efforts have been made in the treatment of cancer, lung cancer is still one of the most fatal malignant kinds of cancers [1, 2]
Gene Ontology (GO) analysis showed that compared with A549 cells, the molecular functions of A549/DDP cells were differently changed: cell cycle, DNA replication, metabolic process, and cellular components had significant changes in cell composition
Through the KEGG results, we found that the PKM2 and LDHA of A549/DDP cells increased 14- and 23- fold (Figure 3C), respectively
Summary
Great efforts have been made in the treatment of cancer, lung cancer is still one of the most fatal malignant kinds of cancers [1, 2]. The best treatment for lung cancer is surgery combined with chemotherapy drugs [3]. Chemotherapy based on cisplatin has greatly improved the prognosis and quality of life of patients with lung cancer. Cisplatin is a kind of chemotherapy drug that can promote DNA damage and induce apoptosis [4,5,6]. Emergence of cisplatin resistance limits its efficacy in lung cancer patients; this has always been a difficult problem. It is of great importance to find new drug combinations to improve the sensitivity of lung cancer cells to cisplatin
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