Int J Stomatol

Int J Stomatol ›› 2025, Vol. 52 ›› Issue (4): 473-483.doi: 10.7518/gjkq.2025062

• Original Articles • Previous Articles     Next Articles

Role of mircoRNA200a/141-signal transduction and transcriptional activator 4 axis in the progression of oral squamous cell carcinoma

Manman Yao(),Yongle Qiu(),Tiejun Liu,Yueting Lu,Hualin Lu,Hongyue Shang,Bo Dong   

  1. Dept. of Stomatology, the Fourth Hospital, Hebei Medical University, Shijiazhuang 050000, China
  • Received:2024-06-10 Revised:2025-01-08 Online:2025-07-01 Published:2025-06-20
  • Contact: Yongle Qiu E-mail:49103567@hebmu.edu.cn;qiuyongle@163.com
  • Supported by:
    Project of the Hebei Provincial Administration of Traditional Chinese Medicine(2024050);Hebei Provincial Natural Science Foundation General Project(H2024206476);Central Government Guides Local Funds Supported by S&T Program of Hebei(246Z7762G)

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Abstract:

Objective　This study aimed to explore the expression and clinical significance of mircoRNA (miRNA) 200a/141 and signal transducer and activator of transcription 4 (STAT4) in oral squamous cell carcinoma (OSCC) and construct a prognostic model to explore its feasibility as a potential therapeutic target. In vitro experiments verified that bionic gelatin exosome particles delivered mi-RNA200a/141 to regulate STAT4. This study also aimed to evaluate the protective capacity and anticancer effects of nucleic acids at the cellular and molecular levels of OSCC. Methods　OSCC-related miRNA-sequencing and messenger RNA-sequencing data were downloaded from The Cancer Genome Atlas database. Data analysis was performed using R language to assess the expression levels and clinical correlation of miRNA200a/141 with STAT4. Biomimetic gelatin exosome nanoparticles (GNP-EXO-mi-RNA200a/141) loaded with miRNA were prepared, and Transwell migration assay, cell scratch assay, and methyl thiazolyl tetrazolium assay were performed to evaluate the effect of nanoparticles on SCC25 cells. The effects of the nanoparticles on STAT4 expression in SCC25 cells were examined using quantitative polymerase chain reaction and Western blot. Results　The expression of miRNA200a/141 was significantly reduced in OSCC tissues, whereas that of its target STAT 4 increased, which was inversely correlated. The prepared GNP-EXO-miRNA200a/141 nanoparticles showed good size distribution and stability. In cell experiments, GNP-EXO-miRNA200a/141 significantly inhibited the proliferation and migration of SCC25 cells and significantly downregulated STAT4 expression. Conclusion　miRNA200a/141 plays an important role in OSCC by regulating STAT4, and it is expected to be a potential molecular marker and therapeutic target for the diagnosis, treatment, and prognosis of OSCC.

Key words: oral squamous cell carcinoma, mircoRNA200a/141, signal transducer and activator of transcription 4, exosomes, gelatin nanoparticles

CLC Number: 

  • R782

TrendMD: 

Fig 1

Preparation model of bionic gelatin EXO particles"

Tab 1

The primer sequence"

基因引物
STAT4

正向引物，5’-AGCCATCTCGGAGGAATA-3’

反向引物，5’-CAGACAACCGGCCTTTAT-3’

GAPDH

正向引物，5’-CGTGGGCCGCCCTAGGCACCA-3’

反向引物，5’-TTGGCTTAGGGTTCAGGGGGG-3’

miRNA-200a

正向引物，5’-TAACACTGTCTGGTAACGATGT-3’

反向引物，5’-ATCGTTACCAGACAGTGTTATT-3’

miRNA-141

正向引物，5’-ACACTCCAGCTGGTAACACTGTCTGGTAA-3’

反向引物，5’-CTCAACTGGTGTCGTGGAGTCGGCA-ATTCAGTT GAGCCATCTTT-3’

Fig 2

Analysis of single gene differences"

Fig 3

Correlation between miRNA200a/141 and STAT4"

Fig 4

Survival analysis of miRNA200a/141 and STAT4 expression and prognosis in patients with OSCC"

Tab 2

Single factor and multiple factor analysis of OSCC prognosis"

特征例数单因素分析多因素分析
风险比（95%置信区间）P值风险比（95%置信区间）P值
年龄/岁<5044参照
≥502151.186（0.691~2.038）0.536
性别男176参照
女831.209（0.805~1.815）0.360
分期Ⅰ期和Ⅱ期64参照
Ⅲ期和Ⅳ期1951.776（1.086~2.905）0.022
T分期T1~T2111参照参照
T3~T41482.269（1.464~3.517）<0.0011.863（1.201~2.891）0.006
N分期N0104参照参照
N1460.526（0.243~1.137）0.1020.574（0.265~1.241）0.158
N2~N31091.847（1.206~2.829）0.0051.451（0.943~2.232）0.090
miRNA-200a高表达82参照
低表达1771.916（1.193~3.076）0.007
miRNA-141高表达86参照参照
低表达1732.298（1.377~3.835）0.0012.077（1.240~3.478）0.005
STAT4低表达153参照参照
高表达1063.016 （2.017~4.511）<0.0012.715（1.809~4.075）<0.001

Fig 5

The characteristic of GNP-EXO and GNP-EXO-miRNA200a/141"

Tab 3

Characterization of nanoparticles"

组别粒径/nmPDI表面电位/mV
GNP109.1±12.10.193±0.05024.53±0.70
GNP-EXO123.1±12.30.216±0.080-11.00±1.20
GNP-EXO-miRNA200a/141127.3±14.00.214±0.030-10.20±0.70

Fig 6

Inhibitory effect of GNP-EXO-miRNA200a/141 nanocomplexes on SCC25 cell growth"

Fig 7

Transwell assay results"

Fig 8

Cell scratch assay results"

Fig 9

STAT4 protein expression in SCC25 cells"

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