miRNA-27b-3p/TPX2 Axis Regulates Clear Cell Renal Cell Carcinoma Cell Proliferation, Invasion and Migration
-
Published:2024
Issue:1
Volume:34
Page:27-39
-
ISSN:1045-4403
-
Container-title:Critical Reviews in Eukaryotic Gene Expression
-
language:en
-
Short-container-title:Crit Rev Eukaryot Gene Expr
Author:
Liu Nana,Jiang Yicheng,Chen Shiyuan,Pan Fang,Tang Yao,Tan Xingping
Abstract
There is a wide variety of cancer cells that can be linked to the presence of TPX2. However, there is not a lot of evidence regarding its role in the development and maintenance of clear cell renal cell carcinoma (ccRCC). In our study, bioinformatics analysis was performed to obtain differentially expressed mRNAs and miR-NAs in ccRCC. Survival curves predicted correlation of TPX2 expression with patient survival. The upstream regulatory miRNA of TPX2 was predicted to be miRNA-27b-3p through database, and dual luciferase assay verified the targeted relationship. qRT-PCR and Western blot were employed for examination of TPX2 mRNA and protein expression in ccRCC cells. Proliferation, invasion, migration and cell cycle were detected by CCK-8, colony formation, wound healing, Transwell, and flow cytometry assays. The results showed that TPX2 showed very high expression in ccRCC, and patients with higher TPX2 expression had shorter relative survival. Low miRNA-27b-3p expression was found in ccRCC. Knockdown of TPX2 or forced expression of miRNA-27b-3p in ccRCC cells inhibited cell proliferation, migration, invasion, and arrested cell division in G<sub>0</sub>/G<sub>1</sub> phase. Dual luciferase reporter presented that miRNA-27b-3p targeted TPX2 to inhibit its expression. Rescue experiments demonstrated that the miRNA-27b-3p/ TPX2 axis affected the biological functions of ccRCC cells. Concurrent overexpression of miRNA-27b-3p and TPX2 inhibited the facilitating effect of TPX2 on ccRCC cell growth. The results revealed novel regulatory mechanisms involved in ccRCC progression, hoping that it may spark an insight for later discovery about the new therapeutic targets for ccRCC.
Subject
Genetics,Molecular Biology
Reference32 articles.
1. Gray RE, Harris GT. Renal cell carcinoma: Diagnosis and management. Am Fam Phys. 2019;99(3):179-84. 2. Capitanio U, Bensalah K, Bex A, Boorjian SA, Bray F, Coleman J, Gore JL, Sun M, Wood C, Russo P. Epidemiology of renal cell carcinoma. Eur Urol. 2019;75(1):74-84. 3. Li Y, Lih TM, Dhanasekaran SM, Mannan R, Chen L, Cieslik M, Wu Y, Lu RJ, Clark DJ, Kolodziejczak I, Hong R, Chen S, Zhao Y, Chugh S, Caravan W, Naser Al Deen N, Hosseini N, Newton CJ, Krug K, Xu Y, Cho KC, Hu Y, Zhang Y, Kumar-Sinha C, Ma W, Calinawan A, Wyczalkowski MA, Wendl MC, Wang Y, Guo S, Zhang C, Le A, Dagar A, Hopkins A, Cho H, Leprevost FDV, Jing X, Teo GC, Liu W, Reimers MA, Pachynski R, Lazar AJ, Chinnaiyan AM, Van Tine BA, Zhang B, Rodland KD, Getz G, Mani DR, Wang P, Chen F, Hostetter G, Thiagarajan M, Linehan WM, Fenyo D, Jewell SD, Omenn GS, Mehra R, Wiznerowicz M, Robles AI, Mesri M, Hiltke T, An E, Rodriguez H, Chan DW, Ricketts CJ, Nesvizhskii AI, Zhang H, Ding L. Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness. Cancer Cell. 2023;41(1):139-63.e17. 4. Abaza R, Gerhard RS, Martinez O. Robotic radical nephrectomy for massive renal tumors. J Laparoendosc Adv Surg Tech A. 2020;30(2):196-200. 5. Ficarra V, Caloggero S, Rossanese M, Giannarini G, Crestani A, Ascenti G, Novara G, Porpiglia F. Computed tomography features predicting aggressiveness of malignant parenchymal renal tumors suitable for partial nephrectomy. Minerva Urol Nephrol. 2021;73(1):17-31.
|
|