Academic Journal
Single-cell transcriptomics and functional analyses identified SPIN.DOC as a regulator for Wnt signaling and cancer stemness in colorectal cancer.
| Τίτλος: | Single-cell transcriptomics and functional analyses identified SPIN.DOC as a regulator for Wnt signaling and cancer stemness in colorectal cancer. |
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| Συγγραφείς: | Devi KM; Department of Biotechnology, Manipur University, Imphal, 795003, India., Abbas E; Department of Molecular Biology and Biotechnology, Tezpur University, Napaam, Tezpur, 784028, Assam, India., Singh TD; Department of Biotechnology, Manipur University, Imphal, 795003, India., Deka R; Department of Molecular Biology and Biotechnology, Tezpur University, Napaam, Tezpur, 784028, Assam, India., Kumar A; Department of Molecular Biology and Biotechnology, Tezpur University, Napaam, Tezpur, 784028, Assam, India., Singh LS; Department of Biotechnology, Manipur University, Imphal, 795003, India., Singh TR; Department of Molecular Biology and Biotechnology, Tezpur University, Napaam, Tezpur, 784028, Assam, India. rthiyam@tezu.ernet.in. |
| Πηγή: | Human cell [Hum Cell] 2026 Aug 19; Vol. 39 (9). Date of Electronic Publication: 2026 Aug 19. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Springer Country of Publication: Japan NLM ID: 8912329 Publication Model: Electronic Cited Medium: Internet ISSN: 1749-0774 (Electronic) Linking ISSN: 09147470 NLM ISO Abbreviation: Hum Cell Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2011- : Tokyo : Springer Original Publication: Tōkyō-to : Hito Saibō Kenkyūkai : Kanishobo, Shōwa 63-nen [1988]- |
| Ιατρικοί όροι (MeSH): | Wnt Signaling Pathway*/genetics , Wnt Signaling Pathway*/physiology , Colorectal Neoplasms*/genetics , Colorectal Neoplasms*/pathology , Neoplastic Stem Cells*/pathology , Single-Cell Analysis*/methods , Gene Expression*/genetics , Carcinogenesis*/genetics , Transcriptome*/genetics, Epithelial-Mesenchymal Transition/genetics ; Cell Proliferation/genetics ; beta Catenin/metabolism ; beta Catenin/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Single-Cell Gene Expression Analysis ; Cell Line, Tumor ; Disease Progression |
| Περίληψη: | The role of SPIN.DOC in tumorigenesis remains unclear. In this study, we utilized single-cell RNA sequencing (scRNA-seq) data to investigate SPIN.DOC expression in a cohort of normal, primary human colorectal cancer (CRC) and metastatic tissues from CRC patients. Our findings revealed differential expressions of SPIN.DOC across multiple cell clusters in different conditions and with the highest expression observed in tumor samples, suggesting its potential role in CRC progression. Further analysis showed that SPIN.DOC positive cell-cluster showed upregulation of β-catenin and cancer stem cell (CSC) marker genes, indicating its role in activating Wnt signaling for cell proliferation. Additionally, these cells also showed downregulation of genes associated with cell-cell junctions, promoting epithelial-mesenchymal transition (EMT) and cancer progression in colon tumors. To validate these findings experimentally, we analyzed the expression of SPIN.DOC in normal colorectal and three colorectal cancer cell lines by immunofluorescence and western blotting. SPIN.DOC was expressed at low level in human normal colon epithelial cells but was highly expressed in all the three colorectal cancer cell lines tested. Consistent with the scRNA data, overexpression of SPIN.DOC in CRC cell line, enhanced cell proliferation, cell migration, invasion, colony-forming capability and Wnt signaling. Moreover, these cells upregulate EMT-associated genes and cancer stem cell markers, as determined by qRT-PCR and immunoblotting. Enhanced spheroid formation in SPIN.DOC overexpressing cells further indicated increased stemness of the cells. Conversely, the knockdown of SPIN.DOC diminished the aforesaid phenotypes. Overall, these data suggest that SPIN.DOC promotes cancer cell proliferation, metastasis and regulates pluripotency and self-renewal of colorectal CSCs. Overall, our study highlights SPIN.DOC as a key essence of CRC by regulating cancer stemness and provides an opportunity of using SPIN.DOC, as a diagnostic and prognostic biomarker of colorectal cancer. (© 2026. The Author(s) under exclusive licence to Japan Human Cell Society.) |
| Competing Interests: | Declarations. Conflict of interest: The authors declare that they have no competing interests. AI declaration: The authors used ChatGPT-4 to improve the readability and language of this manuscript. The content was reviewed and edited by the authors, who take full responsibility for the final version. |
| References: | Int J Oncol. 2014 Mar;44(3):693-9. (PMID: 24365974) Front Immunol. 2019 Dec 16;10:2872. (PMID: 31921137) Transl Cancer Res. 2025 Oct 31;14(10):6497-6519. (PMID: 41234894) BMC Bioinformatics. 2020 May 15;21(1):191. (PMID: 32414321) Oncol Rep. 2016 Jan;35(1):261-6. (PMID: 26498709) Clin Cancer Res. 2021 Sep 1;27(17):4680-4684. (PMID: 33846198) Int J Cancer. 2019 Jun 15;144(12):2992-3000. (PMID: 30536395) Biochem Biophys Res Commun. 2019 Apr 9;511(3):498-503. (PMID: 30803761) J Drug Target. 2024 Dec;32(1):33-44. (PMID: 38095181) Curr Cancer Drug Targets. 2018;18(3):266-277. (PMID: 28669338) Cancer Lett. 2024 Mar 1;584:216664. (PMID: 38253219) Cells. 2023 Dec 28;13(1):. (PMID: 38201271) Genome Biol. 2014;15(12):550. (PMID: 25516281) J Hematol Oncol. 2017 May 5;10(1):101. (PMID: 28476164) J Biol Chem. 2017 Dec 22;292(51):20808-20817. (PMID: 29061846) CA Cancer J Clin. 2020 Jan;70(1):7-30. (PMID: 31912902) Nat Methods. 2019 Dec;16(12):1289-1296. (PMID: 31740819) J Biol Chem. 2020 Dec 4;295(49):16877-16887. (PMID: 32994220) Stem Cells Int. 2021 Jan 6;2021:6667735. (PMID: 33505471) Mol Biol Res Commun. 2025;14(4):283-289. (PMID: 40949799) Int J Mol Med. 2022 Jan;49(1):. (PMID: 34713301) Int J Cancer. 2017 Jun 15;140(12):2709-2715. (PMID: 28281292) J Natl Compr Canc Netw. 2021 Mar 02;19(3):329-359. (PMID: 33724754) Cancer Manag Res. 2023 May 23;15:435-448. (PMID: 37250384) Mol Ther Oncolytics. 2021 May 08;21:183-206. (PMID: 34027052) J Clin Invest. 2011 Mar;121(3):1064-74. (PMID: 21393860) Biomolecules. 2023 Dec 14;13(12):. (PMID: 38136663) Mol Cancer Res. 2024 Apr 2;22(4):337-346. (PMID: 38156967) Signal Transduct Target Ther. 2022 Feb 28;7(1):60. (PMID: 35221332) Nat Biotechnol. 2024 Feb;42(2):293-304. (PMID: 37231261) Cancer Cell. 2023 Jun 12;41(6):1152-1169.e7. (PMID: 37172580) Cancer Gene Ther. 2024 Aug;31(8):1201-1220. (PMID: 38877164) Nat Cell Biol. 2014 Jun;16(6):488-94. (PMID: 24875735) Cell Syst. 2019 Apr 24;8(4):329-337.e4. (PMID: 30954475) Am J Cancer Res. 2020 Mar 01;10(3):727-742. (PMID: 32266087) J Biol Res (Thessalon). 2021 Nov 23;28(1):22. (PMID: 34814951) Epigenetics. 2011 Jan;6(1):9-15. (PMID: 20855937) J Clin Med. 2023 Dec 21;13(1):. (PMID: 38202047) Front Immunol. 2023 Apr 28;14:1148061. (PMID: 37187731) Nat Commun. 2022 Jan 11;13(1):192. (PMID: 35017482) MedGenMed. 2004 Aug 13;6(3):13. (PMID: 15520636) Nat Commun. 2021 Feb 11;12(1):949. (PMID: 33574238) |
| Grant Information: | Internal funding suppport Department of Molecular Biology and Biotechnology, Tezpur University |
| Contributed Indexing: | Keywords: Cancer stem cell; Colorectal cancer; Oncogene; SPIN.DOC; Wnt signalling |
| Substance Nomenclature: | 0 (beta Catenin) |
| Entry Date(s): | Date Created: 20260819 Date Completed: 20260819 Latest Revision: 20261008 |
| Update Code: | 20261008 |
| DOI: | 10.1007/s13577-026-01442-9 |
| PMID: | 42616187 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1749-0774 |
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| DOI: | 10.1007/s13577-026-01442-9 |