Dataset Information

Knockdown THOC2 suppresses the proliferation and invasion of melanoma.

ABSTRACT: Melanoma is a potentially fatal form of skin cancer with great metastatic potential. THOC2 plays a vital role in human biological progression, however, the roles of THOC2 in melanoma tumorigenesis are still unknown. In the present study, our data demonstrated that THOC2 expression was significantly increased in melanoma tissues, and high THOC2 expression was associated with poor overall survival of melanoma patients. THOC2 reduction repressed melanoma cell proliferation and invasion, and induced cell apoptosis in vitro. Microarray data revealed that the cAMP signaling pathway was significantly downregulated in A375 cells transfected with si-THOC2, which was further confirmed by RT-qPCR and bioinformatics analysis. In conclusion, our data indicated that THOC2 might act as an oncogene in melanoma progression through cAMP signaling pathway regulation, which may offer a therapeutic target for melanoma treatment.

SUBMITTER: Zhou X

PROVIDER: S-EPMC7567448 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Knockdown THOC2 suppresses the proliferation and invasion of melanoma.

Zhou Xiaowei X Liu Xing X Zhang Guoqiang G Zhang Qian Q Chen Hao H Wang Yan Y Fang Fang F Sun Jianfang J

Bioengineered 20191201 1

Melanoma is a potentially fatal form of skin cancer with great metastatic potential. THOC2 plays a vital role in human biological progression, however, the roles of THOC2 in melanoma tumorigenesis are still unknown. In the present study, our data demonstrated that THOC2 expression was significantly increased in melanoma tissues, and high THOC2 expression was associated with poor overall survival of melanoma patients. THOC2 reduction repressed melanoma cell proliferation and invasion, and induced ...[more]

PMID: 31680623

Similar Datasets

Project description:Melanoma is the most lethal cutaneous cancer with a high metastatic rate worldwide, causing ~55,500 deaths annually. Although the selective B-Raf oncogene serine/threonine-kinase (BRAF) inhibitors, dabrafenib and vemurafenib, have been approved for the treatment of BRAF-mutant metastatic melanoma, the 5-year survival rate remains unfavorable due to acquired therapy resistance. Therefore, it is of great importance to develop alternative therapeutic drugs and uncover their mechanisms for the treatment of melanoma. 7-dehydrocholesterol (7-DHC) has been demonstrated to inhibit melanoma, but the mechanism is unclear. Therefore, the present study aimed to elucidate the mechanisms of the inhibitory effect of 7-DHC in melanoma cells via analyzing the proliferation, migration, apoptosis, cell cycle and transcriptional sequencing of melanoma cells treated with 7-DHC, as well as constructing a gene signature according to public data of patients with melanoma. In the present study, 7-DHC, the precursor of vitamin D3, was able to induce apoptosis and inhibit cell proliferation and invasion of melanoma cells in a dose-dependent manner. RNA sequencing of melanoma cells treated with different concentrations of 7-DHC revealed that, compared with untreated melanoma cells, 65 genes were downregulated, and genes involved in the regulation of NF-ĸB import into the nucleus and NF-ĸB signaling were significantly repressed. Consistently, the Akt kinase family was one of most common somatic mutation hotspots in patients with melanoma according to The Cancer Genome Atlas enrichment analysis. Furthermore, 7-DHC decreased the phosphorylation of Akt1-Ser473 rather than that of MEK1, and the decreased phosphorylation of Akt1 subsequently inhibited the translocation of free RELA proto-oncogene NF-κB subunit to the nucleus. Finally, by intersecting downregulated genes by 7-DHC treatment and upregulated genes in patients with melanoma, a 7-DHC gene signature was identified, which was negatively associated with the prognosis. Overall, the present results demonstrated that 7-DHC suppressed melanoma cell proliferation and invasion via the Akt1/NF-ĸB signaling pathway, and 7-DHC key target genes were negatively associated with the prognosis. These findings highlight the potential application of 7-DHC for the treatment of melanoma in the future.

Dataset Information

Knockdown THOC2 suppresses the proliferation and invasion of melanoma.

Publications

Knockdown THOC2 suppresses the proliferation and invasion of melanoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets