PMID- 35684411 OWN - NLM STAT- MEDLINE DCOM- 20220613 LR - 20230308 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 27 IP - 11 DP - 2022 May 27 TI - Transcriptome Profiling of HCT-116 Colorectal Cancer Cells with RNA Sequencing Reveals Novel Targets for Polyphenol Nano Curcumin. LID - 10.3390/molecules27113470 [doi] LID - 3470 AB - Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. The gemini nanoparticle formulation of polyphenolic curcumin significantly inhibits the viability of cancer cells. However, the molecular mechanisms and pathways underlying its toxicity in colon cancer are unclear. Here, we aimed to uncover the possible novel targets of gemini curcumin (Gemini-Cur) on colorectal cancer and related cellular pathways. After confirming the cytotoxic effect of Gemini-Cur by MTT and apoptotic assays, RNA sequencing was employed to identify differentially expressed genes (DEGs) in HCT-116 cells. On a total of 3892 DEGs (padj < 0.01), 442 genes showed a log2 FC >|2| (including 244 upregulated and 198 downregulated). Gene ontology (GO) enrichment analysis was performed. Protein-protein interaction (PPI) and gene-pathway networks were constructed by using STRING and Cytoscape. The pathway analysis showed that Gemini-Cur predominantly modulates pathways related to the cell cycle. The gene network analysis revealed five central genes, namely GADD45G, ATF3, BUB1B, CCNA2 and CDK1. Real-time PCR and Western blotting analysis confirmed the significant modulation of these genes in Gemini-Cur-treated compared to non-treated cells. In conclusion, RNA sequencing revealed novel potential targets of curcumin on cancer cells. Further studies are required to elucidate the molecular mechanism of action of Gemini-Cur regarding the modulation of the expression of hub genes. FAU - Azeez, Hewa Jalal AU - Azeez HJ AD - Department of Biology, School of Natural Sciences, University of Tabriz, Tabriz 51368, Iran. FAU - Neri, Francesco AU - Neri F AD - Life Sciences and Systems Biology Department, University of Torino, 10124 Torino, Italy. FAU - Hosseinpour Feizi, Mohammad Ali AU - Hosseinpour Feizi MA AD - Life Sciences and Systems Biology Department, University of Torino, 10124 Torino, Italy. FAU - Babaei, Esmaeil AU - Babaei E AUID- ORCID: 0000-0002-1603-5166 AD - Department of Biology, School of Natural Sciences, University of Tabriz, Tabriz 51368, Iran. LA - eng PT - Journal Article DEP - 20220527 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Polyphenols) RN - IT942ZTH98 (Curcumin) SB - IM MH - *Colonic Neoplasms MH - Computational Biology MH - *Curcumin/pharmacology MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic MH - HCT116 Cells MH - Humans MH - Polyphenols/pharmacology MH - Protein Interaction Maps MH - Sequence Analysis, RNA MH - Transcriptome PMC - PMC9182402 OTO - NOTNLM OT - PPI network OT - RNA sequencing OT - colorectal cancer OT - differentially expressed genes OT - gemini curcumin COIS- The authors declare no conflict of interest. EDAT- 2022/06/11 06:00 MHDA- 2022/06/14 06:00 PMCR- 2022/05/27 CRDT- 2022/06/10 01:24 PHST- 2022/05/01 00:00 [received] PHST- 2022/05/24 00:00 [revised] PHST- 2022/05/24 00:00 [accepted] PHST- 2022/06/10 01:24 [entrez] PHST- 2022/06/11 06:00 [pubmed] PHST- 2022/06/14 06:00 [medline] PHST- 2022/05/27 00:00 [pmc-release] AID - molecules27113470 [pii] AID - molecules-27-03470 [pii] AID - 10.3390/molecules27113470 [doi] PST - epublish SO - Molecules. 2022 May 27;27(11):3470. doi: 10.3390/molecules27113470.