CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma

Ting Li, Si Wu, Lei Jia, et al.

Abstract


Objective: The E3 ligase, CRL4, plays diverse roles in different cellular processes, such as DNA damage, transcriptional regulation,cell cycle progression, and cell apoptosis. Our previous study showed that CUL4A and CUL4B had a strong association with tobaccosmoking risk in lung squamous cell carcinoma (SCC) and small cell lung carcinoma (SCLC). This study aimed to define the potentialmechanism underlying the roles of CUL4A and CUL4B in the development of SCC and SCLC.

Methods: We determined the role of CUL4A and CUL4B in the cell cycle and apoptosis of SCC and SCLC, and identified the keyapoptosis-related gene involved in the oncogenic activity of CUL4B by Western blot, immunohistochemical staining, flow cytometry,and enzyme inhibition experiments.

Results: We found that depletion of CUL4A and CUL4B reduced the proliferation of SCC and SCLC cells. CUL4Aknockdown but notCUL4Bknockdown arrested cells in G1 phase while upregulating P21 and CUL4Bknockdown promoted cell apoptosis through upregulationof FOXO3A. Accordingly, CUL4B decreased FOXO3A expression by activating the ERK signaling pathway and mediating FOXO3Adegradation via the ubiquitin-proteasome pathway.

Conclusions: These results identified the function of E3 ligase CRL4 in regulating SCC and SCLC cell proliferation, which providesa potential strategy for cancer therapy by targeting FOXO3A and the E3 ligase, CRL4.

Cite this article as: Li T, Wu S, Jia L, Cao W, Yao Y, Gang Zhao, et al. CUL4E3 ligase regulates the proliferation and apoptosis of lung squamous cellcarcinoma and small cell lung carcinoma. Cancer Biol Med. 2020; 17: 357-370.doi: 10.20892/j.issn.2095-3941.2019.0107


Keywords


Squamous cell lung cancer; small cell lung cancer; CUL4A; CUL4B; P21; FOXO3A

Full Text: PDF

Refbacks

  • There are currently no refbacks.



OUR FRIENDS