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TRIM44 is indispensable for glioma cell proliferation and cell cycle progression through AKT/p21/p27 signaling pathway

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Abstract

Purpose

Glioma is one of the lethal cancers which needs effective therapeutic target. TRIM44 has been found playing a carcinogenic role in human tumors such as breast cancer and ovarian cancer. However, the pathophysiological significance of TRIM44 in glioma is still unclear.

Methods

Quantitative-PCR and western blot were used to assess the expression of TRIM44 in glioma cells. For cell proliferation, Brdu incorporation and colony formation assays were performed. By Caspase 3 staining and FACS analysis, we revealed that TRIM44 knockdown induced glioma cell apoptosis. A BALB/c nude mouse xenograft model and following immunohistochemical (IHC) staining enables us to explore the effect of TRIM44 deletion on glioma growth in vivo. Western blot of p21, p27 and AKT indicated the possible role of TRIM44 in regulation AKT pathway in glioma.

Results

TRIM44 was significantly elevated in glioma cells, and high expression of TRIM44 is related to poor prognostic of glioma patients. TRIM44 knockdown by shRNAs inhibit glioma cell proliferation, migration, induced cell cycle disruption and further cellular apoptosis in vitro. As well, TRIM44 inactivation obviously inhibit tumor growth in xenograft model. Furthermore, the negative cell cycle regulators p21/p27 are significantly upregulated, while AKT which is known as the main regulator of p21/p27 is inactivated in TRIM44-dificient cells. These results suggested that TRIM44 inactivation disrupted cell cycle progression and inhibit cell proliferation through AKT/p21/p27 pathway in glioma.

Conclusion

TRIM44 was associated with oncogenic potential of glioma. Targeting TRIM44 might be beneficial for glioma therapy.

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Acknowledgements

We thank Ahmed M. Hegazy for manuscript modification. This work was supported by the National Natural Science Foundation of China (NSFC, Grant No. 81472862), the Top Talents Program of Yunnan Province China (Grant No. 2012HA014) to Xudong Zhao, Applied Basic Research Projects of Yunnan (Grant No. 2013FA020), the National Key Research and Development Program of China (Grant Nos. 2016YFC0901701, 2017YFC0908402, 2018YFC0910702, 2018YFC0910402), the China Postdoctoral Science Foundation (Project No: 2019M653500, awarded to Xia Zhou).

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Author notes

  1. Xia Zhou and Yadong Yang contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Central Laboratory of Yan’an Hospital, Affiliated to Kunming Medical University, 245 East Ren Ming Road, Kunming, 650051, Yunnan, China

    Xia Zhou, Qiu Tu & Zongliu Hou

  2. CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing, 100101, China

    Yadong Yang & Xiangdong Fang

  3. University of Chinese Academy of Sciences, Beijing, 100049, China

    Yadong Yang & Xiangdong Fang

  4. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China

    Pengcheng Ma

  5. Oncology and Hematology Department, Mianyang Hospital of T.C.M., Mianyang, 621000, Sichuan, China

    Na Wang

  6. Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, Yunnan, China

    Xia Zhou, Dong Yang, Qiu Tu, Bin Sun & Xudong Zhao

  7. Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Na Wang & Tingxiu Xiang

  8. Kunming Primate Research Center, Chinese Academy of Sciences, Kunming, 650223, Yunnan, China

    Xudong Zhao

  9. KIZ-SU Joint Laboratory of Animal Model and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215000, Jiangsu, China

    Xudong Zhao

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  1. Xia Zhou
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  2. Yadong Yang
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Contributions

XZ and YY performed most experiments of the work. PM helped in the experiment. NW helped with the lentivirus preparation and in vitro experiments. DY, QT, and BS helped with the paraffin section and immunochemical staining. XZ, TX, ZH and XF designed the experiments and wrote the manuscript.

Corresponding authors

Correspondence to Zongliu Hou or Xiangdong Fang.

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Zhou, X., Yang, Y., Ma, P. et al. TRIM44 is indispensable for glioma cell proliferation and cell cycle progression through AKT/p21/p27 signaling pathway. J Neurooncol 145, 211–222 (2019). https://doi.org/10.1007/s11060-019-03301-0

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