Ovarian cancer is a gynecological tumor with an incidence rate lower than those of other gynecological tumor types and the second-highest death rate. CC chemokine 2 (CCL2) is a multifunctional factor associated with the progression of numerous cancers. However, the effect of CCL2 on ovarian cancer progression is unclear. Here, we found that exogenous CCL2 and the overexpression of CCL2 promoted the proliferation and metastasis of ovarian cancer cells. On the other hand, CCL2 knockdown via CRISPR/Cas9 inhibited ovarian cancer cell proliferation, migration, and invasion. The present study demonstrated that mitogen-activated protein three kinase 19 (MAP3K19) was the key CCL2 target for regulating ovarian cancer progression through transcriptome sequencing. Additionally, MAP3K19 knockout inhibited ovarian cancer cell proliferation, migration, and invasion. Furthermore, CCL2 increased MAP3K19 expression by activating the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. The present study showed the correlation between CCL2 and ovarian cancer, suggesting that CCL2 may be a novel target for ovarian cancer therapy.

Upon sensing cytosolic viral RNA, retinoic acid-inducible gene-I-like receptors (RLRs) interact with mitochondrial antiviral signaling proteins (MAVSs) to activate IRF3 and nuclear factor κB (NF-κB) signaling, initiating innate immune responses. Thus, RLR activation plays a vital role in the removal of invasive RNA viruses while maintaining immune homeostasis. However, inadequate or excessive activation of immunity can cause harm and can even lead to lethal consequences. In this study, we identify an E3 ligase, ankyrin repeat and IBR domain containing 1 (ANKIB1), which suppresses RLR signaling via MAVS. ANKIB1 binds to MAVS to enhance K48-linked polyubiquitination with K311R, causing proteasomal degradation of MAVS. Deficiency of ANKIB1 significantly increases the RLR-mediated production of type I interferon (IFN) along with pro-inflammatory factors. Consequently, ANKIB1 deficiency remarkably increases antiviral immunity and decreases viral replication in vivo. Therefore, we reveal that ANKIB1 restricts RLR-induced innate immune activation, indicating its potential role as a therapeutic target for viral infections.

Gynecological cancer is one of the most severe diseases that threaten the lives and health of women worldwide. Its incidence rate increases with each passing year and becomes more prevalent among young people. The prognosis of gynecological cancer remains poor despite significant advances in surgical removal and systemic chemotherapy. Several chemokines play a role in the progression of gynecologic cancers. CCL2 (CC-chemokine ligand 2), also termed MCP-1 (monocyte chemotactic protein 1), plays a significant physiological role in monocyte cell migration and the inflammatory response. Recent studies have demonstrated that CCL2 plays a pro-tumorigenic function in the tumor microenvironment. According to previous studies, CCL2 plays a significant role in the occurrence and development of gynecological cancers. Furthermore, recent studies noted that CCL2 could be a potential diagnostic biomarker and prognostic predictor. The purpose of this paper is to review the role of CCL2 in the occurrence and development of gynecological cancers and to discuss the potential therapeutic strategy of CCL2 for gynecological cancers, with a primary focus on breast cancer, ovarian cancer, cervical cancer, and endometrial cancer.

Cyclophilin A (CypA, also known as PPIA) is an essential member of the immunophilin family. As an intracellular target of the immunosuppressive drug cyclosporin A (CsA) or a peptidyl-prolyl cis/trans isomerase (PPIase), it catalyzes the cis-trans isomerization of proline amidic peptide bonds, through which it regulates a variety of biological processes, such as intracellular signaling, transcription and apoptosis. In this study, we found that intracellular CypA enhanced Twist1 phosphorylation at Ser68 and inhibited apoptosis in A549 cells. Mechanistically, CypA could mediate the phosphorylation of Twist1 at Ser68 via p38 mitogen-activated protein kinase (also known as MAPK14), which inhibited its ubiquitylation-mediated degradation. In addition, CypA increased interaction between Twist1 and p65 (also known as RELA), as well as nuclear accumulation of the Twist1-p65 complex, which regulated Twist1-dependent expression of CDH1 and CDH2. Our findings collectively indicate the role of CypA in Twist1-mediated apoptosis of A549 cells through stabilizing Twist1 protein.

Epithelial ovarian cancer (EOC) is a gynecological tumor with high mortality. Despite aggressive treatment, survival rates for patients with advanced EOC are low, and more effective methods of diagnosis and treatment are urgently needed. Inflammation and cancer are strongly associated; however, the mechanisms that mediate this relationship are not fully understood. In this study, we found that the expression of interleukin-1β (IL-1β), a proinflammatory cytokine, increased in an ovarian cancer tissue microarray (TMA) and inhibited A2780 and SKOV3 cell viability and metastasis. Recombinant IL-1β protein and the overexpression of IL-1β decreased the proliferation and metastasis of ovarian cancer cells. IL-1β deficiency promoted proliferation and metastasis. Moreover, transcriptome sequencing revealed that IL-1β downregulates the expression of matrix metalloproteinase 12 (MMP12). The signaling pathway involving MAPK/AP-1/MMP12 is involved in IL-1β-regulated ovarian cancer progression. Overall, we found that the proinflammatory cytokine IL-1β inhibits ovarian cancer cell viability and metastasis. These findings provided deeper insights into inflammation and cancer progression.