Panoply™ Human TGM2 Knockdown Stable Cell Line

The robust DNA damage repair capacity of cancer cells is a key factor contributing to radioresistance. Previous studies have linked the aberrant expression of transglutaminase 2 (TGM2) to therapeutic resistance. Here, researchers found that TGM2 is significantly upregulated in radioresistant cervical cancer cells and tissues. Knockdown of TGM2 markedly enhances the radiosensitivity of cervical cancer cells, whereas TGM2 overexpression confers radioresistance. TGM2 depletion exacerbates ionizing radiation (IR)-induced DNA double-strand breaks (DSBs). Mechanistic studies reveal that IR triggers the nuclear translocation of TGM2, enabling it to physically interact with POGZ (POGO transposable element-derived zinc finger domain-containing protein) and upregulate POGZ protein levels. TGM2 knockdown impairs the recruitment of BRCA1 to DSB sites, producing phenotypic effects similar to those observed with POGZ knockdown. Rescue experiments confirmed that POGZ knockdown reverses the radioresistance and the reduction in DNA DSBs caused by TGM2 overexpression. A mouse subcutaneous xenograft model further validated these findings in vivo, confirming TGM2's regulatory role in cervical cancer radiosensitivity. In summary, this study demonstrates that TGM2 regulates radiosensitivity through a POGZ-mediated DNA DSB repair process, offering a novel strategy to enhance the radiosensitivity of cervical cancer.

To investigate the functional role of TGM2 in the radiosensitivity of cervical cancer, researchers established TGM2‐knockdown and TGM2‐overexpressing SiHa and MS751 cell lines. Compared with the control groups, TGM2-knockdown SiHa and MS751 cells exhibited significantly reduced survival rates following radiation exposure (Figure 1A, C). Colony formation assays demonstrated that TGM2 knockdown decreased cell survival across various radiation doses (2 Gy, 4 Gy, and 6 Gy), indicating enhanced radiosensitivity in the SiHa and MS751 cell lines (Figure 1B, D). Conversely, the survival rates of TGM2-overexpressing cells were significantly higher than those of control cells at 2 and 3 days post-irradiation (Figure 1E, G). Results from colony formation assays showed that TGM2 overexpression increased cell survival at all tested radiation doses (2 Gy, 4 Gy, and 6 Gy) and conferred radioresistance to the cells (Figure 1F, H).

Figure 1. TGM2 negatively regulates radiosensitivity in cervical cancer cell lines. (Chi Y, et al., 2026)