Overexpressed lncRNA FTX promotes the cell viability, proliferation, migration and invasion of renal cell carcinoma via FTX/miR‑4429/UBE2C axis

Chen,Zhiping; Zhang,Mengting; Lu,Yukang; Ding,Tao; Liu,Zhanyu; Liu,Yanmei; Zhou,Zhaoling; Wang,Lanfeng

doi:10.3892/or.2022.8378

Overexpressed lncRNA FTX promotes the cell viability, proliferation, migration and invasion of renal cell carcinoma via FTX/miR‑4429/UBE2C axis

Authors:
- Zhiping Chen
- Mengting Zhang
- Yukang Lu
- Tao Ding
- Zhanyu Liu
- Yanmei Liu
- Zhaoling Zhou
- Lanfeng Wang
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Affiliations: Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Zhanggong, Ganzhou, Jiangxi 341000, P.R. China, Department of The First Clinical Medical College, Gannan Medical University, Zhanggong, Ganzhou, Jiangxi 341000, P.R. China, Department of Nephrology, First Affiliated Hospital of Gannan Medical University, Zhanggong, Ganzhou, Jiangxi 341000, P.R. China
Published online on: July 21, 2022 https://doi.org/10.3892/or.2022.8378
Article Number: 163
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to explore the role of long non‑coding (lnc)RNA FTX and ubiquitin‑conjugating enzyme E2C (UBE2C) in promoting the progression of renal cell carcinoma (RCC) and the underlying regulatory mechanism. Relative levels of lncRNA FTX, UBE2C, AKT, CDK1 and CDK6 in RCC cell lines were detected by reverse transcription‑quantitative (RT‑q). Expression levels of UBE2C, phosphorylated (p)‑AKT/AKT, p‑CDK1/CDK1 and p‑CDK6/CDK6 in RCC and paracancerous specimens and RCC cells were measured by western blot or immunohistochemistry assay. In addition, the proliferative rate, cell viability, cell cycle progression, migratory rate and invasive rate of RCC cells overexpressing lncRNA FTX by lentivirus transfection were determined by a series of functional experiments, including the colony formation assay, MTT assay, flow cytometry, Transwell assay and wound healing assay. The targeted binding relationship in the lncRNA FTX/miR‑4429/UBE2C axis was validated by dual‑luciferase reporter assay. By intervening microRNA (miR)‑4492 and UBE2C by the transfection of miR‑4429‑mimics or short interfering UBE2C‑2, the regulatory effect of lncRNA FTX/miR‑4429/UBE2C axis on the progression of RCC was evaluated. Finally, a xenograft model of RCC in nude mice was established by subcutaneous implantation, thus evaluating the in vivo function of lncRNA FTX in the progression of RCC. The results showed that lncRNA FTX and UBE2C were upregulated in RCC specimens and cell lines. The overexpression of lncRNA FTX in RCC cells upregulated UBE2C. In addition, the overexpression of lncRNA FTX promoted the cell viability and proliferative, migratory and invasive capacities of RCC cells and accelerated the cell cycle progression. A dual‑luciferase reporter assay validated that lncRNA FTX exerted the miRNA sponge effect on miR‑4429, which was bound to UBE2C 3'UTR. Knockdown of UBE2C effectively reversed the regulatory effects of overexpressed lncRNA FTX on the abovementioned phenotypes of RCC cells. In the xenograft model of RCC, the mice implanted with RCC cells overexpressing lncRNA FTX showed a larger tumor size and higher tumor weight than those of controls, while the in vivo knockdown of UBE2C significantly reduced the size of RCC lesions, indicating the reversed cancer‑promoting effect of lncRNA FTX. Overall, the present study showed that lncRNA FTX was upregulated in RCC and could significantly promote the proliferative, migratory and invasive capacities, enhancing the viability and accelerating the cell cycle progression of RCC cells by exerting the miRNA sponge effect on miR‑4429 and thus upregulating UBE2C. lncRNA FTX and UBE2C are potential molecular biomarkers and therapeutic targets of RCC.

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