RNF135 promotes cell proliferation and autophagy in lung adenocarcinoma by promoting the phosphorylation of ULK1

Main Article Content

Lichun Zhuang
Guanhui Shi
Yuejun Sun

Keywords

Autophagy, Lung Adenocarcinoma, Phosphorylation, Rnf135, Ulk1

Abstract

Objective: To detect the expression of RING finger protein 135 (RNF135) in lung adenocarcinoma tissues and explore its role in the progression of lung adenocarcinoma.


Methods: Bioinformation analysis, quantitative polymerase chain reaction, and immunoblotting technique discovered the expression of RNF135 in lung adenocarcinoma tissues. Cell counting kit-8 and colony formation, immunostaining, and immunoblot assays examined the effects of RNF135 on cell growth and autophagy. Co-immunoprecipitation (Co-IP), immunostaining, and immuoblotting were conducted to confirm the mechanism.


Results: RNF135 was highly expressed in lung adenocarcinoma. In addition, RNF135 promoted lung adenocarcinoma cell growth. Further, data confirmed that RNF135 promoted autophagy in lung adenocarcinoma cells. Mechanically, RNF135 directly interacted with Unc-51-like autophagy activating kinase 1 (ULK1) to promote its phosphorylation level.


Conclusion: RNF135 promoted cell growth and autophagy in lung adenocarcinoma by promoting the phosphorylation of ULK1.

Abstract 273 | PDF Downloads 507 HTML Downloads 0 XML Downloads 7

References

1. Jiang J, Xu Y, Ren H, Wudu M, Wang Q, Song X, et al. MKRN2 inhibits migration and invasion of non-small-cell lung cancer by negatively regulating the PI3K/Akt pathway. J Exp Clin Cancer Res. 2018;37(1):189. 10.1186/s13046-018-0855-7

2. Heller G, Altenberger C, Schmid B, Marhold M, Tomasich E, Ziegler B, et al. DNA methylation transcriptionally regulates the putative tumor cell growth suppressor ZNF677 in non-small cell lung cancers. Oncotarget. 2015;6(1):394–408. 10.18632/oncotarget.2697

3. Das T, Lee EY, You HJ, Kim EE, Song EJ. USP15 and USP4 facilitate lung cancer cell proliferation by regulating the alternative splicing of SRSF1. Cell Death Discov. 2022;8(1):24. 10.1038/s41420-022-00820-0

4. Tritto V, Grilli F, Milani D, Riva P. Deregulated expression of polycomb repressive complex 2 target genes in a NF1 patient with microdeletion generating the RNF135-SUZ12 chimeric gene. Neurogenetics. 2023;24(3):181–8. 10.1007/s10048-023-00718-8

5. Zhang Y, Sui R, Chen Y, Liang H, Shi J, Piao H. Downregulation of miR-485-3p promotes glioblastoma cell proliferation and migration via targeting RNF135. Exp Ther Med. 2019;18(1):475–82. 10.3892/etm.2019.7600

6. Jin J, Zhao L, Li Z. The E3 ubiquitin ligase RNF135 regulates the tumorigenesis activity of tongue cancer SCC25 cells. Cancer Med. 2016;5(11):3140–6. 10.1002/cam4.832

7. Liu Y, Wang F, Liu Y, Yao Y, Lv X, Dong B, et al. RNF135, RING finger protein, promotes the proliferation of human glioblastoma cells in vivo and in vitro via the ERK pathway. Sci Rep. 2016;6:20642. 10.1038/srep20642

8. Lai Y, Liang M, Hu L, Zeng Z, Lin H, Yi G, et al. RNF135 is a positive regulator of IFN expression and involved in RIG-I signaling pathway by targeting RIG-I. Fish Shellfish Immunol. 2019;86:474–9. 10.1016/j.fsi.2018.11.070

9. Chen W, Ni D, Zhang H, Li X, Jiang Y, Wu J, et al. Over-expression of USP15/MMP3 predict poor prognosis and promote growth, migration in non-small cell lung cancer cells. Cancer Genet. 2023;(272–273):9–15. 10.1016/j.cancergen.2023.01.001

10. Lu Y, Qiu Y, Chen P, Chang H, Guo L, Zhang F, et al. ER-localized Hrd1 ubiquitinates and inactivates Usp15 to promote TLR4-induced inflammation during bacterial infection. Nature Microbiol. 2019;4(12):2331–46. 10.1038/s41564-019-0542-2

11. Lin Y, Huang B, He F, Zheng J. BRD4 inhibitor JQ1 may affect the prognosis of cervical cancer through super-enhancer-related genes. Eur J Gynaecol Oncol. 2023;44(5):26–38.

12. Fang XQ, Lee S, Kim YS, Han GE, Lim CH, Lim JH. Streptonigrin mitigates lung cancer-induced cachexia by suppressing TCF4/TWIST1-induced PTHLH expression. Anticancer Res. 2023;43(3):1149–57. 10.21873/anticanres.16260

13. Xiang Y, Duan X, Shao Y, Sun L. NEDD4 activates mitophagy by interacting with LC3 to restrain reactive oxygen species and apoptosis in Apostichopus japonicus challenged with vibrio splendidus. Fish Shellfish Immunol. 2023;141:109037. 10.1016/j.fsi.2023.109037

14. Wang HJ, Li Y, Feng YP, Zhang KW, Peng MD. Protective effects of salidroside on vascular endothelial cells in rats with frostbite after chronic hypoxia. Zhongguo Ying Yong Sheng Li Xue Za Zhi (Chin J Appl Physiol). 2022;38(6):664–9.

15. Liang Q, Guo R, Tsao JR, He Y, Wang C, Jiang J, et al. Salidroside alleviates oxidative stress in dry eye disease by activating autophagy through AMPK-Sirt1 pathway. Int Immunopharmacol. 2023;121:110397. 10.1016/j.intimp.2023.110397

16. Jiang B, Cui Y, Ma X, Zhang Y, Feng X, Yang T, et al. Crosstalk between autophagy inhibitor and salidroside-induced apoptosis: A novel strategy for autophagy-based treatment of hepatocellular cancer. Int Immunopharmacol. 2023;124(Pt B):111040. 10.1016/j.intimp.2023.111040

17. Douglas J, Cilliers D, Coleman K, Tatton-Brown K, Barker K, Bernhard B, et al. Mutations in RNF135, a gene within the NF1 microdeletion region, cause phenotypic abnormalities including overgrowth. Nat Genet. 2007;39(8):963–5. 10.1038/ng2083

18. Wang X, Chen M, Liang X, Bai Y, Zeng J, Xu X, et al. RNF135 promoter methylation is associated with immune infiltration and prognosis in hepatocellular carcinoma. Front Oncol. 2021;11:752511. 10.3389/fonc.2021.752511

19. Ferrari L, Scuvera G, Tucci A, Bianchessi D, Rusconi F, Menni F, et al. Identification of an atypical microdeletion generating the RNF135-SUZ12 chimeric gene and causing a position effect in an NF1 patient with overgrowth. Hum Genet. 2017;136(10):1329–39. 10.1007/s00439-017-1832-5

20. Wang L, Yuan D, Zheng J, Wu X, Wang J, Liu X, et al. Chikusetsu saponin IVa attenuates isoprenaline-induced myocardial fibrosis in mice through activation autophagy mediated by AMPK/m TOR/ULK1 signaling. Phytomed Int J Phytother Phytopharmacol. 2019;58:152764. 10.1016/j.phymed.2018.11.024

21. Xiong R, Li N, Chen L, Wang W, Wang B, Jiang W, et al. STING protects against cardiac dysfunction and remodelling by blocking autophagy. Cell Commun Signal (CCS). 2021;19(1):109. 10.1186/s12964-021-00793-0

22. Ge EJ, Bush AI, Casini A, Cobine PA, Cross JR, DeNicola GM, et al. Connecting copper and cancer: From transition metal signalling to metalloplasia. Nature Rev Cancer. 2022;22(2):102–13. 10.1038/s41568-021-00417-2