Mechanism of translationally-controlled tumor protein 1 in regulating proliferation and migration of renal cell carcinoma cells
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    Abstract:

    Objective To detect the expression of translationally-controlled tumor protein 1 (TPT1) in renal cell carcinoma (RCC) and to explore its role in RCC. Methods Microarray dataset GSE15641 (including 23 normal kidney tissue samples and 32 RCC tissue samples) was downloaded from the Gene Expression Omnibus, and differentially expressed genes between RCC tissue and normal kidney tissue were screened using R 4.3.0 software.The TPT1 expression in RCC tissue and adjacent non-tumor tissue of 90 patients diagnosed and treated at Affiliated Hospital of Nantong University, as well as in human RCC cells (769-P, 786-O, ACHN, and Caki-1) and human embryonic kidney 293 cell (HEK293) was detected by quantitative polymerase chain reaction (qPCR) and Western blotting.The relationship between TPT1 expression and clinical pathological characteristics of RCC patients was analyzed by χ2 test.The clinical data of 522 RCC patients were derived from The Cancer Genome Atlas, and the correlation between TPT1 expression and prognosis of RCC patients was analyzed by receiver operating characteristic (ROC) curve and Kaplan-Meier survival curve.After in vitro transfection of TPT1 small interfering RNA (siRNA) and its negative control (NC) into 786-O and Caki-1 cells, the TPT1 expression was detected by qPCR and Western blotting; the proliferation, migration, and invasion were detected by cell counting kit 8 assay, scratch assay, and Transwell assay, respectively; and the expression of apoptosis-related proteins was detected by Western blotting. Results TPT1 expression was significantly upregulated in the RCC tissue and cells compared with the normal kidney tissue and HEK293 cells (all P<0.05).The RCC patients with low TPT1 expression levels had significantly smaller tumor size and lower metastasis rate than those with high TPT1 expression levels (both P<0.05).The ROC curve analysis results indicated that TPT1 had high diagnostic value for RCC (area under curve was 0.856 9, 95% confidence interval was 0.804 5-0.909 3, P<0.001).The Kaplan-Meier survival analysis results showed that the overall survival of RCC patients in the low TPT1 expression group was significantly longer than that in the high TPT1 expression group (P=0.018 4).In the cell experiment, compared with the siRNA NC group, the proliferation activity, scratch healing rate, and invading transmembrane cell number of 786-O and Caki-1 cells were significantly decreased after transfection with TPT1 siRNA (all P<0.01); the expression levels of B-lymphoma gene 2 (Bcl-2) and matrix metalloproteinase-9 were significantly decreased, while the expression of Bcl-2 associated X protein was significantly increased (all P<0.05). Conclusion TPT1 is involved in the progression of RCC and may be a potential therapeutic target for RCC.

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History
  • Received:July 13,2022
  • Revised:December 12,2022
  • Adopted:
  • Online: December 13,2024
  • Published: December 20,2024
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