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  • br Fig TONSL is involved in TONSL AS

    2019-10-22


    Fig. 6. TONSL is involved in TONSL-AS1 mediated tumor suppressive function.A. Western blotting results revealed that TONSL was successfully interfered in TONSL-AS1 overexpressing and control group.B. CCK-8 experiment was employed to examined the proliferation role of TONSL in TONSL-AS1 overexpressing cells. The statistical results revealed that knockdown TONSL significantly rescue the KCNK15 mediated cell growth inhibition. C. Cell migration and invasion assay revealed that knockdown TONSL significantly rescue the KCNK15 mediated cell motility inhibition. Scar bar: 100 μm.For B and D Mean ± SD were derived from n = 3 independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001; two-tailed unpaired Student's t-test.
    lymph node metastasis (P < 0.05), which indicated that TONSL-AS1 might play an important role in gastric cancer metastasis.
    Recently, lncRNAs was reported to regulate mRNA transcription by interacting with RNA binding proteins, working as a co-activator or suppressor of transcription factors by affecting their target gene's pro-moter [29,30]. TONSL was identified to connect with the 3-prime poly
    (A) tail in eukaryotic mRNA and play an important role in starting translation and shortening poly (A) [31]. TONSL located on chromo-some 8q24.3, was initially identified as the human IκB-R (the inhibitors of NF-κB related) gene. TONSL was thought to be a negative regulator of NF-κB mediated transcription. MMS22L-TONSL associates with re-plication protein A (RPA)-coated ssDNA, and the MMS22L subunit di-rectly interacts with the strand exchange protein RAD51 [32]. TONSL, on the chromosome plus strand, is located downstream from TONSL-AS1 transcription start site. In addition, the Paxilline of TONSL was significantly higher than the other three nearby protein-coding genes (VPS28, CYHR1 and KIFC2) after inducing TONSL-AS1. Furthermore, we found TONSL also inhibited cell proliferation, motility in SGC-7901 and MGC-803 cells. Clinical study revealed a strong correlation between the expression of TONSL and TONSL-AS1. Moreover, overexpression of TONSL-AS1 increased the level of TONSL in SGC-7901 and MGC-803 cells by activating the TONSL promoter. In line with the previous reports, lncRNAs that can affect promoters of coding genes may reg-ulate the expression of coding genes [33]. Taken together, we suggested that TONSL-AS1 increase the expression of TONSL via affecting the promoter of the coding gene. However, the detail way that how TONSL-AS1 affected the promoter of TONSL need more exploration. In general, we showed that a novel lncRNA TONSL-AS1 can inhibit the progression of gastric cancer both in vitro and in vivo by affecting the promoter of TONSL. Additionally, the patients’ clinicopathologic char-acteristics of TONSL-AS1 (Table 1) revealed that TONSL-AS1 sig-nificantly correlated with lymph node metastasis. This suggested that TONSL-AS1 may serve as a biomarker or tumor suppressive molecule in gastric cancer. Although the clinicopathologic characteristics of TONSL are not clear so far, but we strong believe that it may be also important for gastric cancer pathogenesis. We will continue to work on whether TONSL-AS1 can be a potential target in therapies based on TONSL for the treatment of gastric cancer.
    Conflicts of interest
    The authors declare no conflicts of interest.
    Funding
    This work was supported by Promoting Health through Science and Education in Suzhou City Wujiang District (WWK201429), Suzhou Science and Technology Plan Guidance Project (SYSD2016043), Health Care for Cadres in Jiangsu Province (BJ16008). The authors declare that they have no conflict of Interest. Acknowledgements We thank the members of Prof. Yongbin Ding for their technique help.
    References
    M.M. Brodersen, R. Zellweger, A. Sturzenegger, P. Janscak, M. Lopes, M. Peter, P. Cejka, The MMS22L-TONSL heterodimer directly promotes RAD51-dependent recombination upon replication stress, EMBO J. 35 (2016) 2584–2601.