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  • br PIK R phosphoinositide kinase

    2022-05-17


    PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1), is a component of PI3K signaling which is one the most frequently down-regulated pathways in several human cancers, including CRC. Somatic mutation of PIK3R1 was found to promote gliomagenesis [36]. The importance of PI3K signaling in various cancers has made it an at-tractive therapeutic target [37]. In this study, we found that PIK3R1 was upregulated after SNRPA1 knocking down, this upregulation of PIK3R1 contributed to the inhibition of RKO or HCT 116 cell pro-liferation in vitro and ex vivo, which is also reminiscent of previous reports in regard to its role in CRC.
    4. Conclusions
    In summary, the present study suggested that SNRPA1 is an im-portant player in the development or progression of CRCs. The in vitro experiments demonstrated that Knocking down of SNRPA1 by shRNA lentivirus inhibited the cell proliferation, colony formation and pro-moted cell apoptosis in two representative CRC cell line, RKO and HCT116. The ex vivo tumor implantation from shSNRP1 lentivirus transduced RKO ML-210 in nude mice further corroborated these findings. Further microarray gene profiling ML-210 and the western blotting analysis identified a few important oncogenic or tumor suppressor genes regu-lated by SNRPA1 in CRCs. All together, these results showed that SNRPA1 plays an important role in the CRCs by upregulation of NRP1, PIK3R1 and downregulation of E2FZ, VEGFC, MKI67, CDK1 and etc. Our findings identified novel roles of SNRPA1 in CRCs, except its in-volvement in the RNA processing. Those new findings will shed light on future development of new therapeutic targets in the treatment of CRCs.
    Funding
    This study was funded by Shougang Science and Technology Innovation Fund.
    Conflict of interest
    All authors declare that there is no conflict of interest existing re-garding the research, authorship and publication of this manuscript.
    Ethical approval
    All applicable international, national, and/or institutional guide-lines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.
    Acknowledgements
    We thank all the colleagues who participated in this project, Q.M. Zeng, F.M. Lei, Y.G. Chang, Z.C. Gao, Y.Z. Wang, Q.K. Gao, and P.F. Niu all performed in the involved research and helped with manuscript preparation, Q. Li supervised the whole experiment and wrote the final manuscript with approval of all authors.
    Appendix A. Supplementary data
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    Journal of Immunological Methods