NUPR1 is a Novel Potential Biomarker and Confers Resistance to Sorafenib in Clear Cell Renal Cell Carcinoma by Increasing Stemness and Targeting the PTEN/AKT/mTOR Pathway

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2021 May 24

PMID 34030133

Citations 7

Authors

Wei He

Fajuan Cheng

Bin Zheng

Jianwei Wang

Guiting Zhao

Zhongshun Yao

Tong Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Sorafenib can improve the survival of metastatic clear cell renal cell carcinoma (ccRCC) patients. However, its benefits are modest, as patients eventually become resistant, and the mechanisms remain elusive. NUPR1, a stress-induced protein, has been reported in malignancies and functions as an oncogene by modulating the stress response, facilitating survival in harsh environments and conferring drug resistance. However, its role in ccRCC has not been explored.

Methods: The expression and clinical significance of NUPR1 were analyzed in ccRCC patients in in-house patients and The Cancer Genome Atlas (TCGA) cohorts. The biological functions of NUPR1 were investigated. Xenografts were performed to confirm the effects of NUPR1 on tumorigenesis. The molecular mechanism of NUPR1 was investigated and .

Results: NUPR1 expression was upregulated in tumor tissue. Further analysis showed that NUPR1 overexpression was associated with an aggressive phenotype and predicted a poor prognosis. Depletion of NUPR1 suppressed tumorigenesis and sensitized cells to sorafenib treatment. Finally, mechanistic investigations indicated that NUPR1 promoted tumorigenesis in ccRCC by increasing stemness and activating the PTEN/AKT/mTOR signaling pathway.

Conclusions: Collectively, our results suggest that NUPR1 may serve as a predictor of ccRCC. Notably, NUPR1 silencing reversed sorafenib resistance in ccRCC. These findings provide a novel potential therapeutic target in the clinical management of ccRCC.

Citing Articles

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ATF4/NUPR1 axis promotes cancer cell survival and mediates immunosuppression in clear cell renal cell carcinoma.

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Elevated histone deacetylase 10 expression promotes the progression of clear cell renal cell carcinoma by Notch-1-PTEN signaling axis.

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