LLGL2 targets the Hedgehog signaling pathway to influence malignant progression of endometrial cancer.

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Endometrial cancer (EC) is a malignant tumor of the endometrial epithelium, with endometrial adenocarcinoma being the most common type. It has a good overall prognosis, but recurrence and metastasis are often associated with poorer outcomes. LLGL2 is closely linked to tumorigenesis; however, its in endometrial carcinoma is unknown. This study investigated the biological function of LLGL2 in endometrial cancer and its intrinsic molecular mechanisms in promoting the malignant progression of the disease. The expression of LLGL2 in endometrial cancer was analyzed using the TCGA database via UALCAN and validated through western blot analysis, RT-qPCR, and immunohistochemistry. Additionally, the correlation between LLGL2 and the clinicopathological features of patients was examined. The effects of LLGL2 on the proliferation and migration of endometrial cancer cells were assessed using EdU proliferation assay, clone formation assay, Transwell assay, scratch assay, and the detection of proliferation and metastasis markers. Furthermore, the impact of LLGL2 on key genes of the Hedgehog signaling pathway, including SHH, PTCH1, SMO, and GLI1, was explored using western blot analysis and RT-qPCR. The expression of SHH and GLI1 was also detected in cells treated with JK184 in endometrial cancer cells overexpressing LLGL2. Finally, the role of LLGL2 in tumor growth was investigated in vivo using sh-LLGL2 and OE-LLGL2 nude mouse tumorigenic model. LLGL2 expression was upregulated in endometrial cancer tissues compared to normal endometrium. LLGL2 expression was significantly correlated with tumor histological grading (p < 0.01). LLGL2 promoted proliferation, migration, and invasive abilities of endometrial cancer cells. In the nude mouse tumorigenic model, LLGL2 deficiency inhibited the growth of subcutaneously transplanted tumors, and overexpression of LLGL2 promoted the growth of tumors. At the molecular level, LLGL2 may promote the transduction of the Hedgehog signaling pathway in endometrial cancer cells. LLGL2 may be involved in the development of endometrial cancer as an oncogene, leading to aberrant activation of the Hedgehog signaling pathway. Therefore, LLGL2 is a potential new target for the treatment of endometrial cancer.