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Knockdown of LCTL, A Diagnostic Biomarker in Patients with HNSCC, Promotes Apoptosis of HNSCC Cells via the PI3K/Akt Pathway
Vol 37, Issue 5, 2023
Abstract
Background: The Klotho family comprises a series of newly identified anti-aging genes, including α-Klotho (KL), β-Klotho (KLB), and γ-Klotho (LCTL). However, the role of LCTL in the progression of head and neck squamous cell carcinoma (HNSCC) has not been elucidated. Methods: The expression of KL/KLB/LCTL and gene variations in patients with HNSCC were analyzed using the CbioPortal and The Cancer Genome Atlas Program (TCGA) databases. Moreover, KL/KLB/LCTL expression levels in HNSCC tissues were determined using real-time quantitative PCR (Polymerase Chain Reaction) (qPCR) and compared with those in paired non-cancerous adjacent tissues. Cell viability and apoptosis of HNSCC cells were assessed using methylthiazoletetrazolium (MTT) and fluorescence-activated cell sorting assays, respectively. The levels of LCTL and key proteins in the phosphatidylinositol-3-kinase (PI3K)/serine/threonine-protein kinase (Akt) signaling pathway were determined using western blotting. Results: The KL/KLB level was decreased, and the LCTL level was elevated in patients with HNSCC compared with that in normal controls. In addition, the LCTL level was increased in HNSCC cell lines compared with that in human keratinocyte (HACAT) cells. Interference with LCTL significantly suppressed the proliferation of HNSCC cells, promoted apoptosis of SCC (Squamous Cell Carcinoma) 15 cells, and increased the expression of (BCL2 Associated X) Bax and p21 by inhibiting PI3K and Akt phosphorylation. Conclusions: The data suggest that LCTL is a potential diagnostic biomarker for patients with HNSCC. Interference with LCTL significantly suppressed the viability of HNSCC cells and promoted apoptosis of SCC15 cells via the PI3K/Akt signaling pathway.
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Copyright (c) 2023 Yumei Huang, Dianguo Zhao, Changcheng Ding, Xiangrui Ma, Honghai Fu
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Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy