PMID- 34113558 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210612 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 11 DP - 2021 TI - Gene Expression Profile of the Human Colorectal Carcinoma LoVo Cells Treated With Sporamin and Thapsigargin. PG - 621462 LID - 10.3389/fonc.2021.621462 [doi] LID - 621462 AB - Sporamin, a proteinase inhibitor isolated from the sweet potato (Ipomoea batatas), has shown promising anticancer effect against colorectal cancer (CRC) in vitro and in vivo but its mechanisms of action are poorly understood. In the present study, high throughput RNA sequencing (RNA-seq) technology was applied to explore the transcriptomic changes induced by sporamin in the presence of thapsigargin (TG), a non-12-O-tetradecanolphorbol-13-acetate type cancer promoter, in the LoVo human CRC cells. Cellular total RNA was extracted from the cells after they were treated with vehicle (CTL), 1 muM of thapsigargin (TG), or 1 muM of TG plus 30 muM of sporamin (TGSP) for 24 h. The migratory capacity of the cells was determined by wound healing assay. The gene expression profiles of the cells were determined by RNA-seq on an Illumina platform. GO enrichment analysis, KEGG pathway analysis, protein-protein interaction (PPI) network construction, and transcription factors (TF) prediction were all performed based on the differentially expressed genes (DEGs) across groups with a series of bioinformatics tools. Finally, the effect and potential molecular targets of the sporamin at the transcriptome level were evaluated. Sporamin significantly inhibited the migration of cells induced by TG. Among the 17915 genes detected in RNA-seq, 46 DEGs were attributable to the effect of sporamin. RT-PCR experiment validated that the expression of RGPD2, SULT1A3, and BIVM-ERCC5 were up-regulated while NYP4R, FOXN1, PAK6, and CEACAM20 were down-regulated. Sporamin enhanced the mineral absorption pathway, worm longevity regulating pathway, and pyrimidine metabolism pathway. Two TFs (SMIM11A and ATOH8) were down-regulated by sporamin. HMOX1 (up-regulated) and NME1-NME2 (down-regulated) were the main nodes in a PPI network consisting of 16 DEGs that were modulated by sporamin in the presence of TG. Sporamin could favorably alter the gene expression profile of CRC cells, up-regulating the genes that contribute to the homeostasis of intracellular metal ions and the activities of essential enzymes and DNA damage repairment. More studies are warranted to verify its effect on specific genes and delineate the mechanism of action implicated in the process. CI - Copyright (c) 2021 Yang, Chen, Chen, Zhang, Zhang, Xiao and Li. FAU - Yang, Chun AU - Yang C AD - School of Public Health, Capital Medical University (CMU), Beijing, China. AD - Beijing Key Laboratory of Environmental Toxicology, CMU, Beijing, China. AD - Beijing Key Laboratory of Clinical Epidemiology, CMU, Beijing, China. FAU - Chen, Si-Jia AU - Chen SJ AD - School of Public Health, Capital Medical University (CMU), Beijing, China. AD - Beijing Key Laboratory of Environmental Toxicology, CMU, Beijing, China. AD - Beijing Key Laboratory of Clinical Epidemiology, CMU, Beijing, China. FAU - Chen, Bo-Wen AU - Chen BW AD - School of Public Health, Capital Medical University (CMU), Beijing, China. AD - Beijing Key Laboratory of Environmental Toxicology, CMU, Beijing, China. AD - Beijing Key Laboratory of Clinical Epidemiology, CMU, Beijing, China. FAU - Zhang, Kai-Wen AU - Zhang KW AD - School of Public Health, Capital Medical University (CMU), Beijing, China. AD - Beijing Key Laboratory of Environmental Toxicology, CMU, Beijing, China. AD - Beijing Key Laboratory of Clinical Epidemiology, CMU, Beijing, China. FAU - Zhang, Jing-Jie AU - Zhang JJ AD - School of Public Health, Capital Medical University (CMU), Beijing, China. AD - Beijing Key Laboratory of Environmental Toxicology, CMU, Beijing, China. AD - Beijing Key Laboratory of Clinical Epidemiology, CMU, Beijing, China. AD - National Center for Child Nutriment Quality Supervision and Testing, China National Children's Center, Beijing, China. FAU - Xiao, Rong AU - Xiao R AD - School of Public Health, Capital Medical University (CMU), Beijing, China. AD - Beijing Key Laboratory of Environmental Toxicology, CMU, Beijing, China. AD - Beijing Key Laboratory of Clinical Epidemiology, CMU, Beijing, China. FAU - Li, Peng-Gao AU - Li PG AD - School of Public Health, Capital Medical University (CMU), Beijing, China. AD - Beijing Key Laboratory of Environmental Toxicology, CMU, Beijing, China. AD - Beijing Key Laboratory of Clinical Epidemiology, CMU, Beijing, China. LA - eng PT - Journal Article DEP - 20210525 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC8185278 OTO - NOTNLM OT - RNA sequencing OT - colorectal cancer OT - gene expression profile OT - sporamin OT - thapsigargin OT - transcriptome COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/06/12 06:00 MHDA- 2021/06/12 06:01 PMCR- 2021/01/01 CRDT- 2021/06/11 06:46 PHST- 2020/10/26 00:00 [received] PHST- 2021/05/10 00:00 [accepted] PHST- 2021/06/11 06:46 [entrez] PHST- 2021/06/12 06:00 [pubmed] PHST- 2021/06/12 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2021.621462 [doi] PST - epublish SO - Front Oncol. 2021 May 25;11:621462. doi: 10.3389/fonc.2021.621462. eCollection 2021.