Lung cancer is a major cause of death worldwide, with lung adenocarcinoma being the most frequently diagnosed subtype in Japan. Finding the target of an anticancer drug can improve lung adenocarcinoma treatments. Polo-like kinase 1 (PLK1) is an essential mitotic kinase in mitotic progression, and PLK1 inhibition induces cell cycle arrest and apoptosis in tumor cells. In addition, a variety of PLK1 inhibitors have been identified for cancer treatments. In this study, we looked for the target gene of the anticancer drug that has synergy with PLK1 inhibitors. We identified karyopherin beta 1 (KPNB1) as a possible target for lung adenocarcinoma treatment. We found that PLK1 inhibition decreased KPNB1 expression in lung adenocarcinoma cells and KPNB1 depletion inhibited cell proliferation via apoptosis. The same apoptosis signaling pathway may be activated because the expression of common apoptosis-related genes was decreased by PLK1 and KPNB1 silencing; however, the time course of cell growth inhibition was somewhat different. Cell cycle analysis showed that KPNB1 depletion increased the proportion of cells at the G0/G1 phase, although cells also accumulated at the G2/M phase in PLK1-depleted cells. Our findings suggest that decreased KPNB1 expression may be associated with the apoptosis induced by PLK1 inhibition.

Lung cancer is the most common cause of cancer‑associated mortality worldwide, and the number of cases is increasing annually. Several studies have shown that microRNAs (miRNAs) control proliferation, differentiation, and apoptosis in various cell types, and increasing evidence indicates the presence of aberrant miRNA expression profiles and unique miRNA signaling pathways in several types of cancer. The present study aimed to identify miRNAs, which correlated specifically with the progression of lung cancer through the analysis of 57,100 transcripts and 1,341 small RNA expression profiles in 26 lung adenocarcinoma cell lines using next‑generation sequencing. The most marked negative correlation was found between the expression of hsa‑miR‑26a‑1 and messenger RNA (mRNA), and a list of mRNAs, which exhibited negative correlation with hsa‑miR‑26a‑1 were investigated. The most marked negative correlation was observed between the expression levels of hsa‑miR‑26a‑1 and high mobility group A1 (HMGA1). Using a lung adenocarcinoma cell line, the present study analyzed the effect of the overexpression of miR‑26a on the expression of HMGA1 and found that miR‑26a repressed the expression of HMGA1 by reducing the mRNA levels of HMGA1. Furthermore, it was demonstrated that the overexpression of miR‑26a in a lung adenocarcinoma cell line repressed cell migration, invasion and growth by targeting HMGA1. Taken together, the present study showed a significant negative correlation between the expression of miR‑26a and HMGA1 in 26 lung adenocarcinoma cell lines, and provided evidence that the suppression of miR‑26a supports the progression of cancer by stimulating the expression of HMGA1.