Role of TGM2 in T‑cell lymphoblastic lymphoma via regulation of IL‑6/JAK/STAT3 signalling

Wang,Yuyan; Zheng,Ni; Sun,Tingting; Zhao,Hui; Chen,Ying; Liu,Congcong

doi:10.3892/mmr.2022.12592

Role of TGM2 in T‑cell lymphoblastic lymphoma via regulation of IL‑6/JAK/STAT3 signalling

Authors:
- Yuyan Wang
- Ni Zheng
- Tingting Sun
- Hui Zhao
- Ying Chen
- Congcong Liu
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Affiliations: Department of Laboratory, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China
Published online on: January 10, 2022 https://doi.org/10.3892/mmr.2022.12592
Article Number: 76
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Transglutaminase 2 (TGM2) is a Ca²⁺‑dependent enzyme that is closely associated with cancer progression; however, the function of TGM2 in T‑cell lymphoma remains unclear. In the present study, TGM2 was identified as an upregulated gene by bioinformatics analysis of the microarray datasets GSE132550 and GSE143382 from the Gene Expression Omnibus database. The effects and mechanisms of TGM2 on T‑cell lymphoma cells were evaluated using the Cell Counting Kit‑8, colony formation assay, 5‑ethynyl‑2'‑deoxyuridine (EdU) assay, flow cytometry, reverse transcription‑quantitative polymerase chain reaction, western blotting and gene set enrichment analysis (GSEA). TGM2 expression was shown to be elevated in formalin‑fixed paraffin‑embedded skin biopsies from patients with T‑cell lymphoma relative to skin tissue from healthy cases. TGM2 expression was also increased in T‑cell lymphoma cell lines compared with that in CD4⁺ T cells. Transfection with TGM2 small interfering RNAs (siRNAs) decreased the number of EdU‑positive cells, and the viability and colony formation of T‑cell lymphoma cells. Furthermore, TGM2 siRNAs enhanced the apoptosis of T‑cell lymphoma cells potentially via cleavage of caspase‑3 and poly ADP‑ribose polymerase. GSEA identified the IL‑6/JAK/STAT3 pathway as a potential downstream signalling pathway of TGM2. Notably, the effects of TGM2 siRNAs on T‑cell lymphoma cells were attenuated by IL‑6 and accelerated by IL‑6/JAK/STAT3 inhibitor AG490. These findings indicated that TGM2 siRNAs inhibited the proliferation of T‑cell lymphoma cells by regulating the IL‑6/JAK/STAT3 signalling pathway; therefore, TGM2 may function as a potential therapeutic target for T‑cell lymphoma.

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