## 3 Discussion  
MCPIP1 is mainly located in the cytoplasm [37; 38]. Using endonuclease activity in its N-terminal PIN domain, MCPIP1 can cause the degradation of some mRNAs, microRNAs, and viral RNAs to control their half-lives [26]. In addition to the protein-coding mRNAs that play essential functions in the inflammatory process, MCPIP1 also regulates some mRNAs related to the cancer process, thereby affecting cancer proliferation, angiogenesis, metastasis, and apoptosis [27; 39]. Here, we found that MCPIP1 inhibits cell proliferation and promotes cell apoptosis, which was verified by enhanced apoptotic cells in flow cytometry assay and upregulated protein expression of cleaved caspase-3 and PARP1 in a Western blotting assay after MCPIP1 overexpression in cervical cancer cells (Figure 1). Furthermore, we confirmed that the regulatory effect of MCPIP1 on proliferation and apoptosis depends on its endoribonuclease activity because D141N, the MCPIP1 mutant whose endonuclease activity was almost destroyed, failed to increase the apoptotic and floating dead cells after its overexpression (Figure 2). XIAP, an apoptosis inhibitor directly restraining the caspase activity, exhibits an apoptosis inhibitory function in cervical cancer cells because its deficiency leads to upregulated cleaved caspase-3 and PARP1 protein levels (Supplementary Figure S3). Our study identified XIAP as a target of MCPIP1 in exerting its apoptosis-promoting role in cervical cancer cells, which was supported by the findings that the forced expression of XIAP could reverse the pro-apoptotic effect of MCPIP1 on cervical cancer cells (Figure 3). Moreover, it was further revealed that MCPIP1 negatively regulates XIAP mRNA and protein expression by utilizing its endoribonuclease activity. Therefore, our research findings propelled us to conclude that XIAP mediates the apoptosis regulatory role of MCPIP1 in cervical cancer cells. Homeostasis of mRNA levels is determined by the regulation of transcription or mRNA stability. Our study discovered that MCPIP1 weakens the mRNA stability of XIAP, depending on its endonuclease activity (Figure 4) because the D141N mutant of MCPIP1, whose RNase activity was nearly abolished, lost the regulatory effect on XIAP expression. Furthermore, wild-type MCPIP1 but not its C306R mutant could bind with XIAP mRNA and reduce XIAP's mRNA level and stability, indicating that the normal function of the CCCH zinc finger domain of MCPIP1, which mediates the binding of it to XIAP mRNA, is essential for XIAP mRNA decay. Additionally, our in vivo experiments showed that MCPIP1, but not the D141N or C306R mutants, promotes tumor growth in mouse xenograft models, as well as the decreased staining of Ki67 and increased staining of TUNEL in tumor tissues. Collectively, we proposed a working model to show that MCPIP1 binds to XIAP mRNA via its ZF domain and facilitates its degradation by utilizing the endonuclease activity of the PIN domain (Figure 8). As a result, XIAP's protein expression is suppressed in cervical cancer cells, leading to increased cell apoptosis and impediments to cervical cancer development. Cervical cancer is one of the malignant tumors that seriously threaten the health of women worldwide [40]. The treatment for this cancer remains a challenge, with poor clinical prognosis and adverse effects of chemo- and radiotherapy in patients with advanced or recurrent disease [41]. Therefore, exploring new strategies with practical, accurate, and low side effects for cervical cancer treatment is still of great significance. In addition to the finding that MCPIP1 promotes apoptosis and inhibits cervical cancer progression in vivo and in vitro, our study found that the targeted delivery of exogenous MCPIP1 with engineered \(S\). _typhimuriumium_ showed significant inhibition of HeLa tumor growth.