Roles of Krüppel-like factor 6 splice variant 1 in the development, diagnosis, and possible treatment strategies for non-small cell lung cancer.

Krüppel-like factor 6 (KLF6) is a nuclear transcriptional regulator found in mammalian tissue that has been identified as a tumor suppressor gene in several malignancies. As a result of loss of heterozygosity, DNA methylation, and alternative splicing, it is frequently inactivated in various malignancies. Krüppel-like factor 6 splice variant 1 (KLF6-SV1), Krüppel-like factor 6 splice variant 2, and Krüppel-like factor 6 splice variant 3 alternatively spliced isoforms that emerge from a single nucleotide polymorphism in the KLF6 gene. KLF6-SV1 is generally upregulated in multiple cancers, and its biological function is well understood. Overexpression of KLF6-SV1 inhibits the KLF6 gene function while promoting tumor progression, which is associated with a poor prognosis in patients with various malignancies. We reviewed the progress of KLF6-SV1 research in NSCLC over the last several years to understand the molecular mechanisms of tumorigenesis, tumor development, and therapy resistance. Finally, this review emphasizes the therapeutic potential of small interfering RNA targeted silencing of KLF6-SV1 as a novel strategy for managing chemotherapy resistance in NSCLC patients.