# New Diagnostic and Therapeutic Targets for Spinal Cord Injury: GRN Gene

**Authors:** Han Ding, Lei Feng, Jianping Zhang, Tuo Fang, Jun Shang, Ke Fang, Shiqing Feng

PMC · DOI: 10.1111/jcmm.70749 · Journal of Cellular and Molecular Medicine · 2025-07-30

## TL;DR

This study identifies GRN as a potential biomarker for spinal cord injury by analyzing gene expression and immune cell interactions.

## Contribution

The novel contribution is identifying GRN as a potential immune biomarker for SCI through m6A methylation and immune gene correlation analysis.

## Key findings

- 19 constant differentially expressed genes were identified after SCI.
- GRN was found to be a potential immune biomarker for SCI.
- Three subtypes of SCI patients were classified based on gene and immune cell differences.

## Abstract

Spinal cord injury (SCI) is a severe disabling disease due to the poor self‐healing of the central nervous system. Studies showed that many N6‐methyladenosine (m6A) RNA methylation profiles are hypomethylated after SCI, which are related to neural regeneration and different m6A marker genes. In addition, immune cell infiltration may significantly affect the development and progression of SCI. Therefore, we attempted to identify the correlation between SCI‐related biomarkers and m6A methylation regulators in order to classify them. To this end, we collected two gene expression profile datasets (GSE464 and GSE45006) from the GEO database, performed differential expression analysis between pairs before and after SCI, and identified 19 constant differentially expressed genes (DEGs). We found that the constant differential genes were strongly correlated with m6A methylation regulators, which could modulate the immune microenvironment of SCI. Next, this paper used a consensus clustering algorithm to classify SCI patients into three subtypes. There are significant differences between 19 constant DEGs and 28 immune cells among different subtypes. Finally, the correlation analysis of the intersection genes between constant DEGs and immune genes was performed, and GRN was identified as a potential immune biomarker for SCI.

## Linked entities

- **Genes:** GRN (granulin precursor) [NCBI Gene 2896]
- **Diseases:** Spinal cord injury (MONDO:0043797)

## Full-text entities

- **Genes:** aplnrb (apelin receptor b) [NCBI Gene 565492] {aka APLNR2b, Agtrl1a, agtrl1b, grn, zgc:114063}, METTL14 (methyltransferase 14, N6-adenosine-methyltransferase non-catalytic subunit) [NCBI Gene 57721] {aka hMETTL14}, Fdft1 (farnesyl diphosphate farnesyl transferase 1) [NCBI Gene 29580], Rtn4r (reticulon 4 receptor) [NCBI Gene 113912] {aka NgR, NgR1, Nogor}, METTL3 (methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit) [NCBI Gene 56339] {aka IME4, M6A, MT-A70, Spo8, hMETTL3}, Hmgcs1 (3-hydroxy-3-methylglutaryl-CoA synthase 1) [NCBI Gene 29637], Aif1 (allograft inflammatory factor 1) [NCBI Gene 29427] {aka BART-1, Bart1, iba1, mrf-1}, Idi1 (isopentenyl-diphosphate delta isomerase 1) [NCBI Gene 89784], Mir34c (microRNA 34c) [NCBI Gene 100314014] {aka rno-mir-34c}, YTHDF2 (YTH N6-methyladenosine RNA binding protein F2) [NCBI Gene 51441] {aka CAHL, DF2, HGRG8, NY-REN-2}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 25125], MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, Jak2 (Janus kinase 2) [NCBI Gene 24514], CXCL14 (C-X-C motif chemokine ligand 14) [NCBI Gene 9547] {aka BMAC, BRAK, KEC, KS1, MIP-2g, MIP2G}, NOTCH1 (notch receptor 1) [NCBI Gene 4851] {aka AOS5, AOVD1, TAN1, hN1}, Apobec1 (apolipoprotein B mRNA editing enzyme catalytic subunit 1) [NCBI Gene 25383] {aka REPR, apobec-1}, Dlg4 (discs large MAGUK scaffold protein 4) [NCBI Gene 29495] {aka Dlgh4, PSD95, Sap90}, Dlgap2 (DLG associated protein 2) [NCBI Gene 116681] {aka DAP-2, SAPAP2}, S100a4 (S100 calcium-binding protein A4) [NCBI Gene 24615] {aka 18A2, 42A, CAPL, MTS1, P9ka, PEL98}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, MARK1 (microtubule affinity regulating kinase 1) [NCBI Gene 4139] {aka MARK, Par-1c, Par1c}, YTHDF1 (YTH N6-methyladenosine RNA binding protein F1) [NCBI Gene 54915] {aka C20orf21, DF1}, GRN (granulin precursor) [NCBI Gene 2896] {aka CLN11, FTD2, GEP, GP88, PCDGF, PEPI}, Gusb (glucuronidase, beta) [NCBI Gene 24434] {aka Ac2-223, Gus-s}, Csf2 (colony stimulating factor 2) [NCBI Gene 116630] {aka Gm-csf, Gmcsf}, NT-3 [NCBI Gene 4877], P2rx4 (purinergic receptor P2X 4) [NCBI Gene 29659], NTF3 (neurotrophin 3) [NCBI Gene 4908] {aka HDNF, NGF-2, NGF2, NT-3, NT3}, Scd (stearoyl-CoA desaturase) [NCBI Gene 246074] {aka Scd1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, F2r (coagulation factor II (thrombin) receptor) [NCBI Gene 25439] {aka Par1, TRGPC}, Btg1 (BTG anti-proliferation factor 1) [NCBI Gene 29618], Cxcl14 (C-X-C motif chemokine ligand 14) [NCBI Gene 306748] {aka BRAK}
- **Diseases:** tumour (MESH:D009369), inflammation (MESH:D007249), infection (MESH:D007239), ALS (MESH:D000690), swelling (MESH:D004487), AD (MESH:D000544), RD (MESH:D000077733), PD (MESH:D010300), contusion lesions (MESH:D000070624), spinal cord compression injury (MESH:D013117), oesophageal squamous cell carcinoma (MESH:D000077277), spinal cord swelling (MESH:D013118), glioma (MESH:D005910), neuropathic pain (MESH:D009437), anxiety (MESH:D001007), hypersensitivity (MESH:D004342), aneurysm (MESH:D000783), neuroinflammation (MESH:D000090862), neurodegeneration (MESH:D019636), spasms (MESH:D013035), peripheral nerve injury (MESH:D059348), MD (MESH:C535955), lung adenocarcinoma (MESH:D000077192), injury (MESH:D014947), ischaemia (MESH:D007511), contusion (MESH:D003288), PCD (MESH:D007619), hemorrhagic (MESH:D006470), SCI (MESH:D013119), renal injury (MESH:D007674), nervous system diseases (MESH:D009422), function impairment (MESH:D003072), epilepsy (MESH:D004827), intramedullary (MESH:D013120), memory deficits (MESH:D008569), reperfusion injury (MESH:D015427), FTLD (MESH:D057174), autoimmune (MESH:D001327)
- **Chemicals:** isoflurane (MESH:D007530), dopamine (MESH:D004298), chloramphenicol (MESH:D002701), water (MESH:D014867), Ropinirole (MESH:C046649), Quinpirole (MESH:D019257), lipids (MESH:D008055), morphine (MESH:D009020), Cefuroxime sodium (MESH:D002444), epitiostanol (MESH:C002976), CC (-), cholesterol (MESH:D002784), GABA (MESH:D005680), felodipine (MESH:D015736), pronetalol (MESH:C084832), Trizol (MESH:C411644), emetine (MESH:D004640), N6-methyladenosine (MESH:C010223), glutamate (MESH:D018698), pycnogenol (MESH:C024070)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Danio rerio (leopard danio, species) [taxon 7955]
- **Mutations:** C-25 C, G301R

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12309290/full.md

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12309290/full.md

## References

61 references — full list in the complete paper: https://tomesphere.com/paper/PMC12309290/full.md

---
Source: https://tomesphere.com/paper/PMC12309290