Abstract

Purpose Research in this article was performed to explore the biological role and clinical significance of Krüppel-like transcription factor 6 (KLF6) in non-small-cell lung cancer (NSCLC). Methods KLF6 expression in NSCLC cell lines was analyzed using reverse transcription PCR and Western blot. The expressed KLF6 protein was examined in 50 surgical NSCLC tissues using immunohistochemistry. Statistical analyses were employed for clinical association examinations. CCK8 assay and Annexin V/PI analysis were used to execute cell proliferation and apoptosis in KLF6-overexpression cell lines and the control groups. Cleaved caspase-3 expression was also detected in KLF6-overexpression cells and NSCLC tissues. KLF6 expression correlation with cleaved caspase-3 was also examined. Results It was discovered that downregulation of KLF6 was seen in human NSCLC cell lines. Low KLF6 expression in NSCLC tissues was correlated with poor patient prognosis (P < 0.005); patients with less KLF6 expression possessed a lower cumulative 5-year survival rate. Multivariate analysis showed KLF6 expression as an independent prognostic indicator for NSCLC individuals. Expression levels of KLF6 were associated with NSCLC tumor size (P = 0.041). Overexpression of KLF6 inhibited cell proliferation and stimulated A549 and H322 cell line apoptosis. Cleaved caspase-3 protein had higher expression levels in KLF6-overexpressed cells than in the control group. The KLF6 expression levels were positively related to the cleaved caspase-3 protein expression in NSCLC tissues (r = 0.689, P = 0.001). Conclusions The results indicate that downregulation of KLF6 is a significant NSCLC progression marker. KLF6 prevents cell growth and promotes cell apoptosis, possibly caspase-3 activations.

Highlights

  • Lung cancer has long been considered a major basis for death in patients with cancer

  • Krüppel-like transcription factor 6 (KLF6) Was Downregulated in Human Non-small-cell lung cancer (NSCLC) Cell Lines

  • Compared with NHBE, the KLF6 protein expressed in all NSCLC cell lines was reduced (Figures 1(c) and 1(d))

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Summary

Introduction

Lung cancer has long been considered a major basis for death in patients with cancer. Radiotherapy, chemotherapy, and targeted therapy are used as anticancer treatments, lung cancer patients’ 5-year survival rate remains low [3]. Researchers must find new targeted biomarkers for acute diagnosis and effective lung cancer therapy. The Krüppel-like transcription factor (KLF) family, a subfamily of Spl- and Krüppel-like transcription factors, includes a minimum of 25 members in humans. These transcription factors regulate the formation of blood cells [4], angiogenesis [5], lymphocytes [6], tumors [7], and induced pluripotent stem cells [8]. Many studies have shown downregulation, mutation, or inactivation of KLF6 in most cancers, including nasopharyngeal carcinoma [11], astrocytic glioma [12], pituitary tumors [13], gastric cancer [14], colorectal cancer [15], breast cancer [16], hepatocellular carcinoma

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