2. Academic Validation
  3. AL137246.1 inhibits esophageal squamous cell carcinoma cisplatin resistance by suppressing the transcriptional activity of GLI2 on ABCC1

AL137246.1 inhibits esophageal squamous cell carcinoma cisplatin resistance by suppressing the transcriptional activity of GLI2 on ABCC1

  • Mol Genet Genomics. 2025 Oct 14;300(1):96. doi: 10.1007/s00438-025-02298-8.
Lei Song 1,  Limin Zhuang 1,  Ben Ke 2,  Le Wang 3
Affiliations

Affiliations

  • 1 Department of General Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, P.R. China.
  • 2 Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, P.R. China.
  • 3 Departments of Blood Transfusion, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi Province, P.R. China. 15270866233@163.com.
PMID: 41085663 DOI: 10.1007/s00438-025-02298-8
Abstract

Esophageal squamous cell carcinoma (ESCC) is a malignant Cancer. At present, platinum-based chemotherapy drugs are mainly used to treat ESCC patients. However, certain patients have developed significant resistance to cisplatin, which greatly limits the effectiveness of treatment. Hence, it is urgent to probe the mechanism of cisplatin chemotherapy resistance in ESCC. To clarify the association between AL137246.1 level and cisplatin resistance in ESCC patients, a total of 30 pairs of cisplatin-sensitive and cisplatin-resistant ESCC tissues were collected, and 30 non-cancerous tissues were used as controls. Survival analysis was used to detect the relationship between AL137246.1 level and ESCC prognosis. Then, Eca109 and Kyse70 cells were treated with cisplatin to induce the ESCC cisplatin resistance model. For understanding the detailed molecular process involving AL137246.1 in the development of cisplatin resistance in ESCC, the binding relationship between GLI2 and ABCC1 promoter was determined by dual luciferase and ChIP assays. RIP was applied to test the interaction between AL137246.1 and GLI2. Cell viability and proliferation were detected by CCK8 and Edu assays, respectively. Cell Apoptosis was detected by flow cytometry. The results indicated that AL137246.1 level was reduced in ESCC and indicated a poor prognosis of ESCC. AL137246.1 overexpression was associated with increased sensitivity to cisplatin in ESCC cells, which was reversed by ABCC1 upregulation. Mechanistically, GLI2 led to the transcriptional activation of ABCC1 in ESCC. In conclusion, AL137246.1 inhibited the expression of ABCC1 by binding to GLI2, thereby enhancing the sensitivity of ESCC to cisplatin. This study suggested that AL137246.1, as a potential molecular target, has important application prospects in improving the sensitivity of ESCC to cisplatin chemotherapy.

Keywords

ABCC1; AL137246.1; Cisplatin resistance; Esophageal squamous cell carcinoma; GLI2.

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