Long non-coding RNA HOTTIP promotes renal cell carcinoma progression through the regulation of the miR-615/IGF-2 pathway

  • Authors:
    • Qifei Wang
    • Guangzhen Wu
    • Zhiwei Zhang
    • Qizhen Tang
    • Wei Zheng
    • Xiaochi Chen
    • Feng Chen
    • Quanlin Li
    • Xiangyu Che
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  • Published online on: August 23, 2018     https://doi.org/10.3892/ijo.2018.4539
  • Pages: 2278-2288
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Abstract

Emerging evidence has indicated that long non‑coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) regulates cell growth, differentiation, apoptosis and cancer progression. However, the expression and function of HOTTIP in the progression of renal cell carcinoma (RCC) remain largely unknown. In this study, we investigated the role of the lncRNA HOTTIP in RCC. The expression levels of HOTTIP in RCC tissues and cell lines were determined by RT‑qPCR. The association between HOTTIP expression and clinicopathological characteristics and prognosis was analyzed in patients with RCC from the TCGA database. Loss‑of‑ function assays were designed and conducted to verify the oncogenic function of HOTTIP in RCC progression. Luciferase assay was performed to explore the mechanisms of the miRNA‑lncRNA sponge. The results revealed that HOTTIP expression was upregulated in RCC. An increased HOTTIP expression in RCC was associated with a larger tumor size and a higher clinical stage, lymph node metastasis and vascular invasion. Additionally, patients RCC with a high HOTTIP expression had a significantly shorter overall survival (OS) and disease‑free survival (DFS). HOTTIP knockdown significantly inhibited cell proliferation, migration and invasion, and increased the apoptosis of RCC cells in vitro. Mechanistic analyses revealed that HOTTIP functioned as a competing endogenous RNA (ceRNA) for hsa‑miR‑615‑3p, and led to the derepression of its endogenous target, insulin‑like growth factor-2 (IGF‑2), which is a protein hormone that exerts a stimulatory effect on tumor cell growth. miR‑615 inhibition reversed the suppressive effects of HOTTIP knockdown on RCC cell progression. HOTTIP regulated IGF‑2 expression in a miR‑615‑dependent manner in RCC cells. In addition, IGF‑2 expression was significantly upregulated in the RCC specimens and a positive association between the expression of HOTTIP and IGF‑2 in RCC tissues was detected. The effect of HOTTIP was abolished by the siRNA‑mediated silencing of IGF-2 in RCC cells. On the whole, this study demonstrates, for the first time, at least to the best of our knowledge, that the HOTTIP/miR‑615/IGF‑2 axis plays an important role in RCC progression and potentially contributes to the improvement of RCC diagnosis and therapy.
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November-2018
Volume 53 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Wang Q, Wu G, Zhang Z, Tang Q, Zheng W, Chen X, Chen F, Li Q and Che X: Long non-coding RNA HOTTIP promotes renal cell carcinoma progression through the regulation of the miR-615/IGF-2 pathway. Int J Oncol 53: 2278-2288, 2018
APA
Wang, Q., Wu, G., Zhang, Z., Tang, Q., Zheng, W., Chen, X. ... Che, X. (2018). Long non-coding RNA HOTTIP promotes renal cell carcinoma progression through the regulation of the miR-615/IGF-2 pathway. International Journal of Oncology, 53, 2278-2288. https://doi.org/10.3892/ijo.2018.4539
MLA
Wang, Q., Wu, G., Zhang, Z., Tang, Q., Zheng, W., Chen, X., Chen, F., Li, Q., Che, X."Long non-coding RNA HOTTIP promotes renal cell carcinoma progression through the regulation of the miR-615/IGF-2 pathway". International Journal of Oncology 53.5 (2018): 2278-2288.
Chicago
Wang, Q., Wu, G., Zhang, Z., Tang, Q., Zheng, W., Chen, X., Chen, F., Li, Q., Che, X."Long non-coding RNA HOTTIP promotes renal cell carcinoma progression through the regulation of the miR-615/IGF-2 pathway". International Journal of Oncology 53, no. 5 (2018): 2278-2288. https://doi.org/10.3892/ijo.2018.4539