Molecular Characterization and Functional Analysis of Leucine Zipper Transcription Factor Like 1 in Zebrafish (Danio rerio)

Abstract

Leucine zipper transcription factor like 1 (LZTFL1) is a member of the Bardet–Biedl syndrome gene family. LZTFL1-null mice show the phenotype of obesity, retinal degeneration, and abnormal cilia development. Functionally, LZTFL1 serves as a tumor suppressor and a negative regulator in the hedgehog signaling pathways. The biological function of mammalian LZTFL1 is partially addressed, but data on other model organisms are limited. Zebrafish ( Danio rerio ) is widely considered as a powerful model to understand the functions of genes implicated in obesity, disease, and cancer. In this study, LZTFL1 homologs were identified in zebrafish (zebrafish LZTFL1). The full-length cDNA of zebrafish LZTFL1 contained 897 bps encoding 298 amino acids. Zebrafish LZTFL1 displayed conserved domains of coil–coil and leucine zipper domain. PCR results showed that zebrafish LZTFL1 was widely distributed in various tissues. Western blot analysis further revealed that zebrafish LZTFL1 was detected to be ectopically expressed in HeLa cells with correct molecular weight. Fluorescence images showed as well that zebrafish LZTFL1 was localized in the cytoplasm. Furthermore, luciferase reporter assay indicated zebrafish LZTFL1 served as a negative regulator in the hedgehog signaling pathway. These data supported that zebrafish was a good model for understanding the biological roles of LZTFL1.

The Genomic Profile Associated with Risk of Severe Forms of COVID-19 in Amazonian Native American Populations

“…The LZTFL1 gene encodes the leucine zipper transcription factor-like 1, and its function is related to tumor-suppressor action and negative regulation of the hedgehog signaling pathways. In knockout zebrafish (Danio rerio) experimental models, impaired cell traffic in ciliary membranes, retinal degeneration, and obesity were observed [28]. In addition, this gene has high expression in lung tissues; however, the mechanisms directly related to SARS-CoV-2 infection remain unknown [25].…”

“…The LZTFL1 gene encodes the leucine zipper transcription factor-like 1, and its function is related to tumor-suppressor action and negative regulation of the hedgehog signaling pathways. This gene has high expression in lung tissues [25,28]; it is related to the functioning of the cilia of the pulmonary epithelium and to the signaling of important intracellular pathways, regulating the epithelial-mesenchymal transformation [29].…”

Alteration in the expression of microRNA-21 regulated target genes: Role in breast cancer

“…LZTFL-1, a cytoplasmic protein, regulates β-catenin nuclear signaling, ciliary protein trafficking, and the epithelial-mesenchymal transition (EMT) process (Wei et al, 2016). It represses EMT by inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway, which is especially important in lung cancer (Wei et al, 2010;Wei et al, 2019). It functions as a tumor suppressor by stabilizing E-cadherin-mediated adherens junctions and inhibiting β-catenin relocation into the nucleus, preventing cell invasion and EMT-mediated breast cancer metastasis (Wang et al, 2014;.…”