Proteomics

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DNA polymerase POLD1 promotes proliferation and metastasis of bladder cancer by stabilizing MYC

ABSTRACT: Hitherto, most studies on POLD1 have mainly focused on the effect of POLD1 inactivation mutation in tumors. Nonetheless, the mechanism underlying high POLD1 expression in tumorigenesis remains elusive. Herein, we substantiated the pro-carcinogenic role of POLD1 in bladder cancer (BLCA) and found that POLD1 expression is related to malignancy and prognosis of BLCA. Next, we demonstrated that POLD1 could promote proliferation and metastasis of BLCA via MYC. Mechanistically, we demonstrated that POLD1 was able to stabilize MYC in a manner independent of DNA polymerase activity. POLD1 attenuated the FBXW7-mediated ubiquitination degradation of MYC by directly binding to the MYC homology box 1 domain competitively with FBXW7. Moreover, we found that POLD1 can form a complex with MYC to promote the transcriptional activity of MYC. MYC could also transcriptionally activate POLD1, forming a POLD1-MYC positive feedback loop to enhance the pro-carcinogenic effect of POLD1-MYC on BLCA. Overall, our study suggests a novel MYC-driven mechanism for BLCA, and POLD1 has the potential as a biomarker for BLCA.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Yejinpeng Wang  

LAB HEAD: Yu Xiao

PROVIDER: PXD040806 | Pride | 2023-03-29

REPOSITORIES: Pride

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DNA polymerase POLD1 promotes proliferation and metastasis of bladder cancer by stabilizing MYC.

Wang Yejinpeng Y   Ju Lingao L   Wang Gang G   Qian Kaiyu K   Jin Wan W   Li Mingxing M   Yu Jingtian J   Shi Yiliang Y   Wang Yongzhi Y   Zhang Yi Y   Xiao Yu Y   Wang Xinghuan X  

Nature communications 20230427 1

To date, most studies on the DNA polymerase, POLD1, have focused on the effect of POLD1 inactivation mutations in tumors. However, the implications of high POLD1 expression in tumorigenesis remains elusive. Here, we determine that POLD1 has a pro-carcinogenic role in bladder cancer (BLCA) and is associated to the malignancy and prognosis of BLCA. Our studies demonstrate that POLD1 promotes the proliferation and metastasis of BLCA via MYC. Mechanistically, POLD1 stabilizes MYC in a manner indepen  ...[more]

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