SPRR3, a novel miR‑338‑3p target, regulates the malignant progression of clear cell renal cell carcinoma <em>in vitro</em> via the PI3K/Akt signaling pathway

Wu,Man; Guo,Qiaoyan; Liu,Xianjun; Wu,Linlin

doi:10.3892/etm.2022.11246

SPRR3, a novel miR‑338‑3p target, regulates the malignant progression of clear cell renal cell carcinoma in vitro via the PI3K/Akt signaling pathway

Authors:
- Man Wu
- Qiaoyan Guo
- Xianjun Liu
- Linlin Wu
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Affiliations: Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, College of Food Engineering, Jilin Engineering Normal University, Changchun, Jilin 130052, P.R. China
Published online on: March 8, 2022 https://doi.org/10.3892/etm.2022.11246
Article Number: 317
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma and has a poor prognosis. However, its underlying mechanisms remain unclear. The present study aimed to evaluate the role of small proline‑rich repeat protein 3 (SPRR3) in the proliferation, migration and invasion of ccRCC cells and to investigate its upstream and downstream regulatory mechanisms. Survival analysis was performed using the UALCAN website based on the The Cancer Genome Atlas database. Normal renal cell line HK‑2 and ccRCC cell lines (786‑O, CaKi‑1 and UMRC‑2) were used. Reverse transcription‑quantitative PCR (RT‑qPCR) was used to detect mRNA and microRNA (miRNA) levels. Western blotting was used to detect protein levels. Cell Counting Kit‑8 and colony formation assays, a wound healing assay and a Transwell invasion assay were used to assess the proliferation, migration and invasion of ccRCC cells, respectively. Transfection of overexpression plasmids and small interfering RNAs were used to upregulate and knockdown SPRR3 expression, respectively. Transfection of miRNA‑mimics was used to overexpress miR‑338‑3p. A luciferase reporter gene assay was used to verify the predicted binding relationship between SPRR3 mRNA and miR‑338‑3p. The results indicated the following: i) SPRR3 was a risk factor for the survival of patients with ccRCC, and was upregulated in ccRCC cell lines; ii) SPRR3 promoted the proliferation, migration and invasion of ccRCC cells; iii) SPRR3 regulated the tumor phenotypes of ccRCC cells via the PI3K/Akt pathway; iv) miR‑338‑3p directly targeted SPRR3 mRNA and negatively regulated SPRR3 expression; and v) miR‑338‑3p inhibited the PI3K/Akt pathway and the tumor phenotypes of ccRCC cells by downregulating SPRR3. In conclusion, SPRR3, as a novel target of miR‑338‑3p, regulated the proliferation, migration and invasion of ccRCC cells via the PI3K/Akt pathway; this finding not only enriches our understanding of the mechanism underlying ccRCC development, but also demonstrates a potential novel therapeutic target for this disease.

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