Knockdown of long non-coding RNA KCNQ1OT1 depressed chemoresistance to paclitaxel in lung adenocarcinoma

Abstract

Lung cancer, with the highest morbidity and second highest death rates, is one of the most common cancers in both males and females worldwide. Lung adenocarcinoma (LAD) is the main lung cancer class. KCNQ1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1) gene is an lncRNA which had been reported high-expression in colorectal cancer. In this study, the expression of KCNQ1OT1 was confirmed to be highly expressed in LAD tissues and cells contrast to control tissues and cells, and high KCNQ1OT1 expression correlated to malignant behaviors of LAD, including big tumor size, poor differentiation, positive lymphatic metastasis and high TNM stages. The transfection of si-KCNQ1OT1 could effectually knockdown the expression of KCNQ1OT1 in A549 and A549/PA cells. The KCNQ1OT1 knockdown depressed the proliferation and invasion of A549 cells, and advanced cellular apoptosis of A549 cells. The expression of KCNQ1OT1 in LAD patients insensitive to paclitaxel was much higher than that in LAD patients sensitive to paclitaxel; the KCNQ1OT1 expression in A549/PA cells was also much higher than that in control A549 cells. The half maximal inhibitory concentration (IC50) of paclitaxel in A549/PA cells was depressed by KCNQ1OT1 knockdown, chemoresistance of A549/PA cells was inhibited significantly. KCNQ1OT1 knockdown also depressed the expression of multidrug resistance 1 (MDR1) protein in A549/PA cells. In summary, lncRNA KCNQ1OT1 was highly expressed in LAD and functioned as a potential oncogene to inhibit malignancy and chemoresistance of LAD cells, which might be a novel potential therapeutic target for LAD.

RNA sequencing reveals PNN and KCNQ1OT1 as predictive biomarkers of clinical outcome in stage III colorectal cancer patients treated with adjuvant chemotherapy

“…KCNQ1OT1 also reached statistical significance in the validation set after multivariate analysis. Higher expression levels of KCNQ1OT1 have been shown in tissues from solid tumors including colorectal cancer, and lung adenocarcinoma compared to normal mucosa. Interestingly, high mRNA expression levels of KCNQ1OT1 were correlated with paclitaxel resistance in lung cancer patients.…”

“…Interestingly, high mRNA expression levels of KCNQ1OT1 were correlated with paclitaxel resistance in lung cancer patients. Also, in vitro silencing of KCNQ1OT1 in paclitaxel‐resistant A549/PA cells restored paclitaxel sensitivity . In CRC, an aberrant expression and function of KCNQ1OT1 have been reported .…”

LncRNA KCNQ1OT1 Mediates Pyroptosis in Diabetic Cardiomyopathy

“…The lncRNA Kcnq1ot1, the full name of which is KCNQ1 overlapping transcript 1, is located in the KCNQ1 locus at 11p15.5 [13]. Kcnq1ot1 has been reported to be associated with many disorders, particularly those related to heart disease [14][15][16][17]. Li et al [14] indicated that suppression of Kcnq1ot1 might prevent myocardial I/R injury following acute myocardial infarction via regulating AdipoR1.…”

The Dysregulated Expression of KCNQ1OT1 and Its Interaction with Downstream Factors miR-145/CCNE2 in Breast Cancer Cells

“…At present, few studies regarding its aberrant expression and function in cancers have been reported. Ren et al revealed that KCNQ1OT1 played an oncogenic role in regulating malignant behavior and chemoresistance of lung adenocarcinoma cells [19]. Sunamura et al indicated that regulation of KCNQ1OT1 lncRNA by β-catenin signaling might be involved in multiple processes of colorectal cancer development [20].…”