CDK5RAP1 targeting NF-κB signaling pathway in human malignant melanoma A375 cell apoptosis

Xiong,Jikui; Wang,Yan; Gu,Yanli; Xue,Yadong; Dang,Lin; Li,Yuzhen

doi:10.3892/ol.2018.7920

CDK5RAP1 targeting NF-κB signaling pathway in human malignant melanoma A375 cell apoptosis

Authors:
- Jikui Xiong
- Yan Wang
- Yanli Gu
- Yadong Xue
- Lin Dang
- Yuzhen Li
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Affiliations: Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Department of Pathology, Heilongjiang Provincial Hospital, Harbin, Heilongjiang 150036, P.R. China, Department of Dermatology, Daqing Oilfield General Hospital, Daqing, Heilongjiang 163000, P.R. China, Department of Dermatology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Published online on: February 1, 2018 https://doi.org/10.3892/ol.2018.7920
Pages: 4767-4774
Copyright: © Xiong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Malignant melanoma is characterized by rapid deterioration, early metastasis and high mortality. Cdk5 regulatory subunit‑associated protein 1 (CDK5RAP1), which catalyzes 2‑methylthio (ms2) modification of mitochondrial transfer RNAs, has been reported to induce cancer cell apoptosis, by a phospho‑c‑Jun N‑terminal kinase (p‑JNK) signaling pathway. The present study was the first to report on the association between CDK5RAP1 deficiency and nuclear factor‑κB (NF‑κB) signaling pathway during the apoptosis process in human malignant melanoma (A375) cells. CDK5RAP1 small interfering RNA (siRNA) and control siRNA were transfected into A375 cells. CDK5RAP1 deficiency inhibited Ca2+ influx in A375 cells. CDK5RAP1 deficiency also suppressed the proliferation of A375 cells, induced A375 cells apoptosis, and increased the generation of reactive oxygen species (ROS). In addition, CDK5RAP1 deficiency induced the phosphorylation of NF‑κB and Bcl‑2/Bcl‑xl‑associated death promoter (Bad). Notably, the phosphorylation of B‑cell lymphoma‑xl (Bcl‑xl) and B‑cell lymphoma‑2 (Bcl‑2) was downregulated by CDK5RAP1 deficiency. Pretreatment with pyrrolidine dithiocarbamate (PDTC), the inhibitor of NF‑κB, prevented the decrease in cell proliferation and apoptosis induced by CDK5RAP1 deficiency in A375 cells. However, pretreatment with PDTC did not affect the generation of ROS in A375 cells, indicating that ROS is an upstream target of NF‑κB signaling pathway during the apoptosis process. Taken together, CDK5RAP1 deficiency induces cell apoptosis in malignant melanoma A375 cells via the NF‑κB signaling pathway. The results from the present study indicated a potential novel candidate for the treatment of skin cancer.

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