Panoply™ Human STAT3 Over-expressing Stable Cell Line

Dysregulation of Pol III products contributes to various diseases, including neurological disorders and cancer. Despite significant progress in the field, the specific factors and mechanisms governing Pol III-mediated transcription remain to be fully elucidated. Here, researchers demonstrate that STAT3 positively regulates Pol III-dependent transcriptional activity and cancer cell growth. RNA-seq analysis reveals that STAT3 suppresses the expression of TP73, a member of the p53 family. TP73 is identified not only as an essential factor in STAT3-regulated Pol III-mediated transcription but also as an independent inhibitor of Pol III product synthesis. Mechanistically, TP73 disrupts TFIIIB subunit assembly and inhibits TFIIIB binding to Pol III target sites by interacting with the TFIIIB subunit TBP. MiR-106a-5p activates Pol III-mediated transcription by targeting the 3' untranslated region (3' UTR) of TP73 mRNA to reduce TP73 expression. The researchers further demonstrate that STAT3 activates miR-106a-5p expression by binding to its promoter, indicating that miR-106a-5p serves as a link between STAT3 and TP73 in the regulation of Pol III-mediated transcription. Collectively, these findings indicate that STAT3 positively regulates Pol III-mediated transcription by modulating the miR-106a-5p/TP73 axis.

It is well established that the levels of Pol III products are closely linked to cell growth or proliferative activity. However, it remains unclear whether STAT3-mediated changes in Pol III products affect cell proliferation. In this study, researchers first analyzed the proliferative activity of STAT3-knockdown or STAT3-overexpressing HepG2 cell lines using cell counting and CCK-8 assays. The results showed that STAT3 silencing reduced the proliferation of HepG2 cells (Figure 1A and B), whereas STAT3 overexpression promoted it (Figure 1C and D). Similar results were observed in STAT3-knockdown or STAT3-overexpressing HuH-7 and 293T cell lines. EdU (5-ethynyl-2'-deoxyuridine), a deoxyuridine analog that is readily incorporated into newly synthesized DNA, is widely used to assess cell proliferation. Accordingly, the researchers further examined the effect of altered STAT3 expression levels on EdU labeling efficiency in HepG2 cells. The results demonstrated that STAT3 depletion reduced the proportion of EdU-labeled cells (Figure 1E and F), while STAT3 upregulation increased this proportion, suggesting that STAT3 promotes the proliferative activity of liver cancer cells.

Figure 1. STAT3 promotes cell growth in vitro. (Zhang C, et al., 2023)