OncoTargets and Therapy (Oct 2020)

ITPKA1 Promotes Growth, Migration and Invasion of Renal Cell Carcinoma via Activation of mTOR Signaling Pathway

  • Zhu X,
  • Xu A,
  • Zhang Y,
  • Huo N,
  • Cong R,
  • Ma L,
  • Chu Z,
  • Tang Z,
  • Kang X,
  • Xian S,
  • Xu X

Journal volume & issue
Vol. Volume 13
pp. 10515 – 10523

Abstract

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Xiang Zhu,1,2,* An Xu,3,* Yang Zhang,4,* Nan Huo,2 Rui Cong,2 Luyuan Ma,2 Zhong Chu,2 Zhi Tang,2 Xiaofeng Kang,2 Shaozhong Xian,5 Xiaojie Xu2 1Department of Infectious Disease, Army No.82 Group Military Hospital, Baoding, People’s Republic of China; 2Department of Cellular Engineering Lab, Beijing Institute of Biotechnology, Beijing, People’s Republic of China; 3Department of Oncology, Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 5Department of Urology, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaojie Xu; Shaozhong Xian Email [email protected]; [email protected]: Renal cell cancer (RCC) is one of the most lethal malignancies of the kidney in adults. mTOR (mammalian target of rapamycin) signaling pathway plays a pivotal role in RCC tumorigenesis and progression and inhibitors targeting the mTOR pathway have been widely used in advanced RCC treatment. Therefore, it is of great significance to explore the potential regulators of the mTOR pathway as RCC therapeutic targets.Materials and Methods: Bioinformatics analysis was used to screen out the most significant differentially expressed genes in the RCC dataset of The Cancer Genome Atlas (TCGA). Real-time PCR and Western-blot analysis were utilized to examine the expression of inositol-1,4,5-trisphosphate-3-kinase-A (ITPKA) in four RCC cell lines and one human embryonic kidney cell line. Cell counting Kit-8 and colony formation assay were performed to estimate the effect of ITPKA on the proliferation ability of RCC cells. Wound healing and Transwell assays were used to test the effect of ITPKA on RCC cell migration and invasion. Xenograft formation assay was performed in nude mice to investigate the effect of ITPKA in vivo. mTORC1 pathway inhibitor was added to explore the mechanisms by which ITPKA regulates RCC cell growth and progression.Results: Based on bioinformatics analysis, ITPKA is screened out as one of the most significant differentially expressed genes in RCC. ITPKA is upregulated and positively correlated with RCC malignancy and poorer prognosis. ITPKA promotes RCC growth, migration and invasion in cultured cells, and accelerates tumor growth in nude mice. Mechanistically, ITPKA stimulates the mTORC1 signaling pathway which is a requirement for ITPKA modulation of RCC cell proliferation, migration and invasion.Conclusion: Our data demonstrate a critical regulatory role of the ITPKA in RCC and suggest that ITPKA/mTORC1 axis may be a promising target for diagnosis and treatment of RCC.Keywords: ITPKA1, RCC, growth, migration and invasion, mTORC1 pathway

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