Background <p>CircRNAs have a potential regulatory effect on Renal cell carcinoma (RCC). However, there is still a significant lack of research on their action pathways and mechanisms in the treatment of RCC. The aim of this study is to identify the effects of Circ_001024 on the proliferation, migration, and invasion of RCC cells, and to elucidate the molecular mechanisms by which Circ_001024 promotes the malignant biological behaviors of RCC cell lines.</p> Methods <p>The expression of Circ_001024 in RCC was detected using quantitative real-time polymerase chain reaction (qRT-PCR) To confirm Circ_001024’s structure and properties, tests using Sanger sequencing, RNase R, and actinomycin D were performed. The localization in RCC cells was identified using the Fluorescence in situ hybridization (FISH) assay. Bioinformatics analysis, Spearman correlation analysis, dual-luciferase reporter assay, and RNA pull-down assay were used to verify the interactions among Circ_001024, its targeted miR-145-3p, and the targeted protein GLUT5,and these interactions were further validated by rescue experiments. In addition, Western blot (WB) was used to detect the expression changes of the signaling pathway target protein GLUT5, and the clinicopathological characteristics of GLUT5 in RCC were analyzed.</p> Results <p>The gene Circ_001024 showed high expression levels in RCC, predominantly found in the cytoplasm of RCC cells. Forced expression of Circ_001024 accelerated RCC progression by enhancing cell proliferation, migration, and invasion, whereas Circ_001024 knockdown elicited the reverse effects. miR-145-3p could interact with both Circ_001024 and the targeted protein GLUT5. Overexpression of miR-145-3p could partially reverse the changes in the proliferation, migration, and invasion abilities caused by overexpression of Circ_001024. Moreover, the expression of GLUT5 was associated with the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade, but not with age, gender, tumor diameter, or TNM staging.</p> Conclusion <p>Circ_001024 is highly expressed in RCC. Within RCC, Circ_001024 can promote the proliferation, migration, and invasion of RCC cells through the competitive inhibition of miR-145-3p, which controls GLUT5 expression.</p> Graphical Abstract <p></p>

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Role and mechanism of circ_001024 endogenous competition for miR-145-3p targeting to regulate GLUT5 in RCC

  • Lanlan Zhao,
  • Jieyu Xu,
  • Dandan Li,
  • Yao Chen,
  • Qingqing Fu,
  • Xiaorong Yang,
  • Jian Zhang

摘要

Background

CircRNAs have a potential regulatory effect on Renal cell carcinoma (RCC). However, there is still a significant lack of research on their action pathways and mechanisms in the treatment of RCC. The aim of this study is to identify the effects of Circ_001024 on the proliferation, migration, and invasion of RCC cells, and to elucidate the molecular mechanisms by which Circ_001024 promotes the malignant biological behaviors of RCC cell lines.

Methods

The expression of Circ_001024 in RCC was detected using quantitative real-time polymerase chain reaction (qRT-PCR) To confirm Circ_001024’s structure and properties, tests using Sanger sequencing, RNase R, and actinomycin D were performed. The localization in RCC cells was identified using the Fluorescence in situ hybridization (FISH) assay. Bioinformatics analysis, Spearman correlation analysis, dual-luciferase reporter assay, and RNA pull-down assay were used to verify the interactions among Circ_001024, its targeted miR-145-3p, and the targeted protein GLUT5,and these interactions were further validated by rescue experiments. In addition, Western blot (WB) was used to detect the expression changes of the signaling pathway target protein GLUT5, and the clinicopathological characteristics of GLUT5 in RCC were analyzed.

Results

The gene Circ_001024 showed high expression levels in RCC, predominantly found in the cytoplasm of RCC cells. Forced expression of Circ_001024 accelerated RCC progression by enhancing cell proliferation, migration, and invasion, whereas Circ_001024 knockdown elicited the reverse effects. miR-145-3p could interact with both Circ_001024 and the targeted protein GLUT5. Overexpression of miR-145-3p could partially reverse the changes in the proliferation, migration, and invasion abilities caused by overexpression of Circ_001024. Moreover, the expression of GLUT5 was associated with the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade, but not with age, gender, tumor diameter, or TNM staging.

Conclusion

Circ_001024 is highly expressed in RCC. Within RCC, Circ_001024 can promote the proliferation, migration, and invasion of RCC cells through the competitive inhibition of miR-145-3p, which controls GLUT5 expression.

Graphical Abstract