KANK1 regulates paclitaxel resistance in lung adenocarcinoma A549 cells

Abstract

Paclitaxel (PTX), a tubulin-binding agent, is widely used and has shown good efficacy in the initial period of treatment for non-small cell lung cancer (NSCLC). However, the relatively rapid acquisition of resistance to PTX treatments that is observed in virtually all cases significantly limits its utility and remains a substantial challenge to the clinical management of NSCLC. The aim of this study was to identify candidate genes and mechanisms that might mediate acquired paclitaxel resistance. In this work, we established paclitaxel-resistant cells (A549-T) from parental cell lines by step-dose selection in vitro. Using methylation chip analysis and transcriptome sequencing, 43,426 differentially methylated genes and 2,870 differentially expressed genes are identified. Six genes (KANK1, ALDH3A1, GALNT14, PIK3R3, LRG1, WEE2), which may be related to paclitaxel resistance in lung adenocarcinoma, were identified. Among these genes, KANK1 exhibited significant differences in methylation and expression between cell lines. Since KANK1 plays an important role in the development of renal cancer and gastric cancer, we hypothesised that it may also play a role in acquired resistance in lung adenocarcinoma. Transient transfection of SiKANK1 significantly reduced the expression of KANK1, reducing apoptosis, increasing cell migration, and enhancing the tolerance of A549 cells to paclitaxel. KANK1 acts as a tumour suppressor gene, mediating the resistance of lung adenocarcinoma A549 to paclitaxel. The reduction of KANK1 expression can increase the paclitaxel resistance of non-small cell lung cancer and increase the difficulty of clinical treatment.

APC Promoter Methylation in Gastrointestinal Cancer

“…Resistance to therapeutic drugs is a significant challenge affecting survival and prognosis for patients receiving medical treatment. Relevant studies have shown that, when a certain gene was abnormally methylated, the abnormal expression of that gene and resistance to anti-tumor drugs would develop (74)(75)(76)(77). Shen et al reported that decreased expression of the tumor suppressor gene KANK1 could increase paclitaxel resistance in non-small cell lung cancer (75).…”

“…Relevant studies have shown that, when a certain gene was abnormally methylated, the abnormal expression of that gene and resistance to anti-tumor drugs would develop (74)(75)(76)(77). Shen et al reported that decreased expression of the tumor suppressor gene KANK1 could increase paclitaxel resistance in non-small cell lung cancer (75). In CRC, NKX6.1 gene was demonstrated to participate in the regulation of chemotherapy sensitivity for its hypermethylation (78).…”

lncRNA GAS5 enhances tumor stem cell-like medicated sensitivity of paclitaxel and inhibits epithelial-to-mesenchymal transition by targeting miR-18a-5p/STK4 pathway in prostate cancer

“…Paclitaxel is a routine taxane-type chemotherapy drug for many cancers [5,6], including PCA [7]. Like in many other cancers [8,9], paclitaxel chemoresistance is a common problem existing in the process of PCA treatment [10]. That will result in the recurrence and metastasis of PCA, leading to poor survival of the patients.…”

Digital Image Analysis Applied to Tumor Cell Proliferation, Aggressiveness, and Migration-Related Protein Synthesis in Neuroblastoma 3D Models

“…DOCK8 is involved in cytoskeleton remodeling, inducing migration in macrophages, Schwann precursors cells, T cells, and dendritic cells [31][32][33][34]. KANK1 participates in actin and microtubule regulation; however, its role in inhibiting or promoting migration depends on the system studied [35][36][37][38]. It has also been reported to play a role as a tumor suppressor gene [39,40].…”