Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Nov 17;15(22):13059-13076.
doi: 10.18632/aging.205219. Epub 2023 Nov 17.

Inhibition of UFM1 expression suppresses cancer progression and is linked to the dismal prognosis and immune infiltration in oral squamous cell carcinoma

Di Ke  1 , Hao-Han Guo  2 , Ni Jiang  3 , Rong-Shu Shi  1 , Teng-Yang Fan  4
Affiliations

Inhibition of UFM1 expression suppresses cancer progression and is linked to the dismal prognosis and immune infiltration in oral squamous cell carcinoma

Di Ke et al. Aging (Albany NY). .

Abstract

Background: Ubiquitin fold modifier 1 (UFM1) overexpression is associated with cancer cell proliferation, migration and invasion. However, the roles and pathways of UFM1 in oral squamous cell carcinoma (OSCC) has remained undefined.

Methods: The expression of UFM1 and the relationship between UFM1 expression and prognosis were investigated using data of OSCC patients from The Cancer Genome Atlas (TCGA) database. The UFM1 co-expressed genes, and the association between the UFM1 expression and immune cells and ubiquitination were explored. The effects of UFM1 expression on the growth and migration of OSCC cells were investigated by siRNA interference, Cell Counting Kit-8 (CCK-8), Transwell, Western blotting, and wound healing experiments.

Results: UFM1 was highly expressed in OSCC. UFM1 overexpression was associated with short overall survival, disease-specific survival, and progression-free interval, and was an adverse factor for prognosis in OSCC. UFM1-related nomograms were significantly associated with poor prognosis in OSCC patients. Decreased UFM1 expression could inhibit the proliferation, migration, and invasion of OSCC cells. UFM1 was associated with the immune cells (such as the Th17 cells, T helper cells, and cytotoxic cells) and ubiquitination.

Conclusion: Elevated UFM1 expression was associated with poor prognosis, ubiquitination and immune infiltration in OSCC, and inhibition of UFM1 expression delayed OSCC progression, showing that UFM1 could be a biomarker for prognosis and treating OSCC patients.

Keywords: OSCC; UFM1; biomarkers; immune cells; ubiquitination.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
UFM1 expression significantly increased in OSCC tissues of the TCGA database. (A) The data of TPM type in TCGA database; (B) The data of FPKM type in TCGA database. Note: OSCC, oral squamous cell carcinoma; TCGA, The Cancer Genome Atlas; FPKM, reads per kilobase of transcript per million reads mapped; TPM, transcripts per million.
Figure 2
Figure 2
The relationship between UFM1 expression and dismal prognosis was explored based on the status of cancer patients in TCGA database. (A) OS; (B) DSS; (C) PFI. Note: OS, overall survival; DSS, disease-specific survival; PFI, progression-free interval.
Figure 3
Figure 3
Elevated UFM1 expression levels associated with dismal prognosis in OSCC patients based on the data of TPM type in TCGA database. (A) OS; (B) DSS; (C) PFI. Note: OSCC, oral squamous cell carcinoma; TPM, transcripts per million; OS, overall survival; DSS, disease-specific survival; PFI, progression-free interval; TCGA, The Cancer Genome Atlas.
Figure 4
Figure 4
Elevated UFM1 expression associated with the shorter OS in OSCC patients based on the data of TPM type in TCGA database. (A) Stage T1-3; (B) Stage T2-3; (C) Stage T2-4; (D) Stage T3; (E) Stage T3-4; (F) Stage T4; (G) N1-2; (H) N1-3; (I) N2; (J) N2-3; (K) M0. Note: OSCC, oral squamous cell carcinoma; OS, overall survival; TPM, transcripts per million; TCGA, The Cancer Genome Atlas.
Figure 5
Figure 5
Elevated UFM1 expression associated with the shorter DSS in OSCC patients based on the data of TPM type in TCGA database. (A) Stage T1-3; (B) Stage T2-3; (C) Stage T2-4; (D) Stage T3; (E) Stage T3-4; (F) N0; (G) N1-2; (H) N1-3; (I) N2; (J) N2-3; (K) M0. Note: OSCC, oral squamous cell carcinoma; DSS, disease-specific survival; TPM, transcripts per million; TCGA, The Cancer Genome Atlas.
Figure 6
Figure 6
Elevated UFM1 expression associated with the shorter PFI in OSCC patients based on the data of TPM type in TCGA database. (A) Stage T1-2; (B) Stage T1-3; (C) Stage T2-3; (D) Stage T2-4; (E) Stage T3; (F) Stage T3-4; (G) N0; (H) N1-2; (I) N1-3; (J) N2; (K) N2-3; (L) M0. Note: OSCC, oral squamous cell carcinoma; PFI, progression-free interval; TPM, transcripts per million; TCGA, The Cancer Genome Atlas.
Figure 7
Figure 7
The OS, DSS and PFI-related nomograms based on the T, N, and M stages and UFM1 expression based on the data of TPM type in TCGA database. (A) OS; (B) DSS; (C) PFI. Note: OS, overall survival; DSS, disease-specific survival; PFI, progression-free interval; TPM, transcripts per million; TCGA, The Cancer Genome Atlas.
Figure 8
Figure 8
UFM1 co-expressed genes were shown using scatter plot. (A) SUPT20H; (B) COG6; (C) COG3; (D) MTRF1; (E) GPALPP1; (F) WBP4; (G) USPL1; (H) ALG5; (I) ALG11; (J) NUP58; (K) N4BP2L2; (L) CDK8.
Figure 9
Figure 9
Inhibiting UFM1 expression significantly reduces cell proliferation and invasion via CCK-8 and Transwell. (A–C) Establishment of cell model; (D) Cell proliferation; (E) Cell invasion.
Figure 10
Figure 10
Inhibition of UFM1 expression significantly reduces cell migration. (A) Wound healing of cancer cells; (B) Cell migration rate in si-UFM1 vs. NC groups.
Figure 11
Figure 11
UFM1 expression correlation with immune infiltrating cells in OSCC using bubble plot. Note: OSCC, oral squamous cell carcinoma.
Figure 12
Figure 12
UFM1 expression correlated with immune infiltrating cells in OSCC using scatter plot. (A) Th17 cells; (B) T helper cells; (C) Tgd; (D) Tcm; (E) Cytotoxic cells; (F) pDC. Note: OSCC, oral squamous cell carcinoma.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Liu J, Cao W, Chen W, Xu L, Zhang C. Decreased expression of Kallmann syndrome 1 sequence gene (KAL1) contributes to oral squamous cell carcinoma progression and significantly correlates with poorly differentiated grade. J Oral Pathol Med. 2015; 44:109–14. 10.1111/jop.12206 - DOI - PubMed
    1. Xu L, Li Q, Wang Y, Wang L, Guo Y, Yang R, Zhao N, Ge N, Wang Y, Guo C. m6A methyltransferase METTL3 promotes oral squamous cell carcinoma progression through enhancement of IGF2BP2-mediated SLC7A11 mRNA stability. Am J Cancer Res. 2021; 11:5282–98. - PMC - PubMed
    1. Mao L, Wu X, Gong Z, Yu M, Huang Z. PDIA6 contributes to aerobic glycolysis and cancer progression in oral squamous cell carcinoma. World J Surg Oncol. 2021; 19:88. 10.1186/s12957-021-02190-w - DOI - PMC - PubMed
    1. Huang Y, Chen Z, Chen X, Chen X, Xu M. TOMM34 promotes cell proliferation, migration, and invasion of OSCC and modulates mitochondrial function. J Oral Pathol Med. 2023; 52:47–55. 10.1111/jop.13382 - DOI - PubMed
    1. Zhang G, Zhao X, Liu W. NEDD4L inhibits glycolysis and proliferation of cancer cells in oral squamous cell carcinoma by inducing ENO1 ubiquitination and degradation. Cancer Biol Ther. 2022; 23:243–53. 10.1080/15384047.2022.2054244 - DOI - PMC - PubMed

Publication types