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Lung cancer is the most common cause of cancer‑associated mortality. MicroRNAs (miRNAs), as oncogenes or tumor suppressor genes, serve crucial roles not only in tumorigenesis, but also in tumor invasion and metastasis. Although miRNA‑let‑7a (let‑7a) has been reported to suppress cell growth in multiple cancer types, the biological mechanisms of let‑7a in lung adenocarcinoma are yet to be fully elucidated. In the present study, the molecular roles of let‑7a in lung adenocarcinoma were investigated by detecting its expression in lung adenocarcinoma tissues and exploring its roles in the regulation of lung cancer cell proliferation. Let‑7a expression was identified to be downregulated in lung adenocarcinoma tissues compared with normal tissues. Overexpression of let‑7a effectively suppressed cancer cell proliferation, migration and invasion in H1299 and A549 cells. Let‑7a also induced cell apoptosis and cell cycle arrest. Furthermore, let‑7a significantly inhibited cell growth by directly regulating cyclin D1 signals. This novel regulatory mechanism of let‑7a in lung adenocarcinoma provides possible avenues for future targeted therapies of lung cancer.

MicroRNAs (miRNAs or miRs) have recently become a popular focus of cancer research due to their ability to act as oncogenes or tumor suppressors. In the present study, miR‑33a‑5p expression was identified to be downregulated in lung adenocarcinoma samples compared with normal, which suggested that miR‑33a‑5p may serve as a tumor suppressor gene. Transfection with miR‑33a‑5p mimics inhibited the proliferation and migration of A549 and LTEP‑a‑2 cells and increased cellular apoptosis. A luciferase reporter assay confirmed that miR‑33a‑5p targets the 3'‑untranslated region of the mechanistic target of rapamycin (mTOR) gene. mTOR expression was decreased in A549 and LTEP‑a‑2 cells treated with miR‑33a‑5p mimics, as well as the expression of its downstream effectors phosphorylated (p)‑p70 ribosomal protein S6 kinase (p70S6K) and p‑eukaryotic translation initiation factor 4E binding protein 1 (4EBP1). Following treatment with celastrol, miR‑33a‑5p expression was upregulated, and miR‑33a‑5p could enhance cellular sensitivity to celastrol. Western blot analysis revealed that the expression of mTOR, p‑p70S6K and p‑4EBP1 decreased following celastrol treatment. These results suggested that mTOR was involved in the mechanism by which miR‑33a‑5p enhanced the sensitivity of lung adenocarcinoma cells to celastrol. Furthermore, LTEP‑a‑2 cells were xenografted subcutaneously into nude mice, to examine the effect of celastrol and miR‑33a‑5p on the growth of LTEP‑a‑2 cells in vivo. The results demonstrated that tumor growth in the celastrol‑treated or miR‑33a‑5p‑treated group was attenuated compared with the control group. Notably, tumor growth in the combination treatment group was almost arrested after 2 weeks. In addition, celastrol upregulated the expression of miR‑33a‑5p, and high expression of miR‑33a‑5p inhibited mTOR and its downstream effectors. In summary, miR‑33a‑5p inhibited the proliferation of lung adenocarcinoma cells, enhanced the antitumor effect of celastrol, and improved sensitivity to celastrol by targeting mTOR in lung adenocarcinoma in vitro and in vivo.