OTX1 promotes tumorigenesis and progression of cervical cancer by regulating the Wnt signaling pathway

Abstract

Cervical cancer is a common malignant tumor in females. Orthodenticle homolog 1 (OTX1) serves a key role in the occurrence and progression of tumors. The present study aimed to investigate the role and potential mechanism of OTX1 in cervical cancer. OTX1 expression was analyzed by western blotting, reverse transcription-quantitative PCR and immunohistochemistry. MTT assay was performed to assess cell viability. EdU and colony formation assay were used to measure cell proliferation. Wound healing and Transwell assays were performed to measure cell migration and invasion. Western blot assay was performed for the assessment of protein expression. Gene set enrichment analysis (GSEA) was performed to analyze signaling pathways regulated by OTX1. Co-Immunoprecipitation assay was performed to confirm the interaction between OTX1 and Wnt9b. In cervical cancer tissue and cells, OTX1 was significantly upregulated. OTX1 overexpression promoted proliferation, migration and invasion of cervical cancer cells. OTX1 silencing significantly decreased cell proliferation, migration and invasion of cervical cancer. GSEA showed that OTX1 activated the Wnt signaling pathway. OTX1 silencing inhibited the increased levels of adenomatous polyposis coli (APC), glycogen synthase kinase (GSK)-3β and axis inhibition protein (AXIN)2 and decreased levels of Wnt9b and β-catenin. OTX1 overexpression decreased the levels of APC, GSK-3β and AXIN2 and increased levels of Wnt9b and β-catenin. However, XAV939 (a Wnt signaling inhibitor) and β-catenin silencing partly eliminated the effect of OTX1 overexpression on cervical cancer cells. OTX1 promoted the progression of cervical cancer by activating the Wnt signaling pathway.

Integrated transcriptome and cell phenotype analysis suggest involvement of PARP1 cleavage, Hippo/Wnt, TGF-β and MAPK signaling pathways in ovarian cancer cells response to cannabis and PARP1 inhibitor treatment

“…Downstream to MAPK signaling and FGFR signaling (hsa04550) is OTX1, a bicoid-like homeodomain transcription factor ( Zhou et al, 2022 ). Expression of OTX1 was significantly upregulated in cervical cancer tissue and cells, promoting cell proliferation, migration, and invasion ( Zhou et al, 2022 ). It was suggested that by activating the Wnt signaling pathway, OTX1 promoted the progression of cervical cancer ( Zhou et al, 2022 ).…”

“…Expression of OTX1 was significantly upregulated in cervical cancer tissue and cells, promoting cell proliferation, migration, and invasion ( Zhou et al, 2022 ). It was suggested that by activating the Wnt signaling pathway, OTX1 promoted the progression of cervical cancer ( Zhou et al, 2022 ). OTX1 gene expression was repressed by F7 or the combined treatment in both cell lines.…”

“…FGFR2 gene expression was repressed by the combined treatment in Caov3 in particular. Downstream to MAPK signaling and FGFR signaling (hsa04550) is OTX1, a bicoid-like homeodomain transcription factor (Zhou et al, 2022). Expression of OTX1 was significantly upregulated in cervical cancer tissue and cells, promoting cell proliferation, migration, and invasion (Zhou et al, 2022).…”

Stemness Landscape and Its Clinical Implications in Hepatocellular Carcinoma

“…The expression of AOC1 was signi cantly reduced in HCC tumor tissues [32]. Studies have demonstrated that OTX1 promotes tumor progression in various cancer types, including pancreatic, breast, laryngeal squamous cell carcinoma, gastric, colorectal, hepatocellular, and cervical cancers [33][34][35][36][37][38][39]. CASC9 has been shown to promote laryngeal carcinoma, oral squamous cell carcinoma, retinoblastoma, bladder cancer, and non-small cell lung cancer [40][41][42][43][44].…”

Orthodenticle Homeobox OTX1 Promotes Papillary Thyroid Carcinoma Progression and Is a Potential Prognostic Biomarker

“…Similarly, in lung cancer, abnormal OTX1 expression has been associated with enhanced invasion capability of tumor cells, contributing to metastasis [ 12 ]. In addition, an aberrant OTX1 level has been indicated in cervical cancer progression [ 13 ].…”