SKA2-mediated transcriptional downregulation of the key enzyme of CoQ10 biosynthesis PDSS2 in lung cancer cells

作者全名："Xia, Xing; Tao, Chuntao; Du, Kailong; Meng, Peixin; Hu, Lanyue; Cheng, Dong; Liu, Xianjun; Bu, Youquan; Fan, Xiaoyan; Chen, Quanmei"

作者地址："[Xia, Xing; Tao, Chuntao; Du, Kailong; Meng, Peixin; Hu, Lanyue; Cheng, Dong; Liu, Xianjun; Bu, Youquan; Chen, Quanmei] Chongqing Med Univ, Coll Basic Med Sci, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China; [Xia, Xing; Tao, Chuntao; Du, Kailong; Meng, Peixin; Hu, Lanyue; Cheng, Dong; Liu, Xianjun; Bu, Youquan; Chen, Quanmei] Chongqing Med Univ, Coll Basic Med Sci, Mol Med & Canc Res Ctr, Chongqing 400016, Peoples R China; [Fan, Xiaoyan] Taizhou Univ, Dept Basic Med Sci, 1139 Shifu Rd, Taizhou 318000, Zhejiang, Peoples R China; [Chen, Quanmei] Chongqing Med Univ, Dept Biochem & Mol Biol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Fan, XY (通讯作者)，Taizhou Univ, Dept Basic Med Sci, 1139 Shifu Rd, Taizhou 318000, Zhejiang, Peoples R China.; Chen, QM (通讯作者)，Chongqing Med Univ, Dept Biochem & Mol Biol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：JOURNAL OF CANCER

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000994381300001

JCR分区：Q2

影响因子：3.3

年份：2023

卷号：14

期号：2

开始页：322

结束页：335

文献类型：Article

关键词：SKA2; PDSS2; transcription regulation; lung cancer

摘要："Lung cancer is the leading cause of cancer-associated mortality worldwide. SKA2 is a novel cancer-associated gene that plays critical roles in both cell cycle and tumorigenesis including lung cancer. However, the molecular mechanisms underlying its implication in lung cancer remains elusive. In this study, we first analyzed the gene expression profiling after SKA2 knockdown, and identified several candidate downstream target genes of SKA2, including PDSS2, the first key enzyme in CoQ10 biosynthesis pathway. Further experiments verified that SKA2 remarkably repressed PDSS2 gene expression at both mRNA and protein levels. Luciferase reporter assay showed that SKA2 repressed PDSS2 promoter activity through its Sp1-binding sites. Co-immunoprecipitation assay demonstrated that SKA2 associated with Sp1. Functional analysis revealed that PDSS2 remarkably suppressed lung cancer cell growth and motility. Furthermore, SKA2-induced malignant features can be also significantly attenuated by PDSS2 overexpression. However, CoQ10 treatment showed no obvious effects on lung cancer cell growth and motility. Of note, PDSS2 mutants with no catalytic activity exhibited comparable inhibitory effects on the malignant features of lung cancer cells and could also abrogate SKA2-promoted malignant phenotypes in lung cancer cells, highly suggesting a non-enzymatic tumor-suppressing activity of PDSS2 in lung cancer cells. The levels of PDSS2 expression were significantly decreased in lung cancer samples, and lung cancer patients with high expression of SKA2 and low expression of PDSS2 displayed remarkable poor prognosis. Collectively, our results demonstrated that PDSS2 is a novel downstream target gene of SKA2 in lung cancer cells, and the SKA2-PDSS2 transcriptional regulatory axis functionally contributes to human lung cancer cell malignant phenotypes and prognosis."

基金机构：National Nature Science Foundation of China [81802289]; Innovation and Entrepreneurship [202210350060]

基金资助正文："This research was supported by the National Nature Science Foundation of China (No. 81802289 to QC) , National Training Program for College Students? Innovation and Entrepreneurship (No. 202210350060 to XF) ."