<p>PLK1 contributes to autophagy by regulating MYC stabilization in osteosarcoma cells</p>

Abstract

BackgroundPLK1, a typical PLK protein, is the main driver of cancer cell growth and proliferation. It is an inhibitor of the protein kinases that is currently being investigated in clinical studies. It is often used as a tumor marker, as high PLK1 expression correlates with poor prognosis in cancer. Overexpression of MYC is a hallmark of many human cancers. MYC modulates the transcription of thousands of genes that required to coordinate a series of cellular processes, including those essential for growth, proliferation, differentiation, self-renewal and apoptosis. To date, functions of PLK1 and MYC on tumor are mostly studied in separate researches, and studies on their mutual crosstalk are lacking.PurposeTo investigate the mechanism of PLK1 and MYC in regulating progress of osteosarcoma.MethodsProtein level was examined using Western blot. Animal experiments were performed with female FOX CHASE severe combined immunodeficient mice. Mice were randomly divided into experimental or control groups.ResultsPLK1 or MYC promoted the proliferation of osteosarcoma cells through the autophagy pathway. PLK1 contributed to MYC protein stabilization. PLK1 inhibition enhanced MYC degradation in osteosarcoma cells. PLK1 inhibition led to a marked decline in MYC protein abundance. The representative MYC target genes were deregulated by PLK1 inhibitors. BI2536 treatment caused a significant delay in xenograft tumor growth in mice injected with U-2 OS cells subcutaneously, with lower mean tumor weight compared to the control group.ConclusionPLK1 is crucial for MYC stabilization. It promotes cell proliferation by autophagy pathway in osteosarcoma cells. Data validate PLK1 as a potential therapeutic target in osteosarcoma caused by MYC-amplified.

<p>MiR-1224-5p Activates Autophagy, Cell Invasion and Inhibits Epithelial-to-Mesenchymal Transition in Osteosarcoma Cells by Directly Targeting PLK1 Through PI3K/AKT/mTOR Signaling Pathway</p>

“…36 Mo et al found that PLK1 could promote the proliferation of MYC-amplifying OS cells through autophagy. 37 These results are consistent with our research results. It is suggested that miR-1224-5p regulates the effect of PLK1 expression on the occurrence and development in OS.…”

Crizotinib Resistance Mediated by Autophagy Is Higher in the Stem-Like Cell Subset in ALK-Positive Anaplastic Large Cell Lymphoma, and This Effect Is MYC-Dependent

“…In 2003, Tsuneoka et al demonstrated that the overexpression of MYC in rat fibroblasts significantly increased the number of autophagic vacuoles [ 44 ]. In a more recent study, it was found that the loss of MYC can reduce autophagy and further restrain cellular proliferation in osteosarcoma cells [ 45 ]. Thus, results from these two studies support the concept that MYC can regulate autophagy.…”

Gene signatures with predictive and prognostic survival values in human osteosarcoma

“…Moreover, the MYC gene is also reported to be amplified in a subset of OS ( Ladanyi et al, 1993 ). MYC promotes the proliferation of OS cells through the autophagy pathway ( Mo et al, 2019 ). Cross-species genomics identified DLG2 as a tumor suppressor in OS ( Shao et al, 2019 ).…”