Gynecological and breast cancers are a group of heterogeneous malignant tumors. Although existing treatment strategies have ameliorated the clinical outcomes of patients, the overall survival rate of advanced diseases remains unsatisfactory. Increasing evidence has indicated that the development and prognosis of tumors are closely related to the tumor microenvironment (TME), which restricts the immune response and provokes malignant progression. Tumor-associated macrophages (TAMs) are the main component of TME and act as a key regulator in tumor metastasis, immunosuppression and therapeutic resistance. Several preclinical trials have studied potential drugs that target TAMs to achieve potent anticancer therapy. This review focuses on the various functions of TAMs and how they influence the carcinogenesis of gynecological and breast cancers through regulating cancer cell proliferation, tumor angiogenesis and tumor-related immunosuppression. Besides, we also discuss the potential application of disabling TAMs signaling as a part of cancer therapeutic strategies, as well as CAR macrophages, TAMs-based vaccines and TAMs nanobiotechnology. These research advances support that targeting TAMs combined with conventional therapy might be used as effective therapeutics for gynecological and breast cancers in the future.

N 6 -Methyladenosine (m 6 A), a pervasive posttranscriptional modification which is reversible, has been among hotspot issues in the past several years. The balance of intracellular m 6 A levels is dynamically maintained by methyltransferase complex and demethylases. Meanwhile, m 6 A reader proteins specifically recognize modified residues and convey messages so as to set up an efficient and orderly network of m 6 A regulation. The m 6 A mark has proved to affect every step of RNA life cycle, from processing in nucleus to translation or degradation in cytoplasm. Subsequently, disorders in m 6 A methylation are directly related to aberrant RNA metabolism, which results in tumorigenesis and altered drug response. Therefore, uncovering the underlying mechanism of m 6 A in oncogenic transformation and tumor progression seeks opportunities for novel targets in cancer therapy. In this review, we conclude the extensive impact of m 6 A on RNA metabolism and highlight its relevance with human cancer, implicating the far-reaching value in clinical application.

Inflammation is a defense mechanism that can protect the host against microbe invasion. A proper inflammatory response can maintain homeostasis, but continuous inflammation can cause many chronic inflammatory diseases. To properly treat inflammatory disorders, the molecular mechanisms underlying the development of inflammation need to be fully elucidated. Pyroptosis is an inflammation-related cell death program, that is different from other types of cell death. Pyroptosis plays crucial roles in host defense against infections through the release of proinflammatory cytokines and cell lysis. Accumulating evidence indicates that pyroptosis is associated with inflammatory diseases, such as arthritis, pneumonia, and colonitis. Furthermore, pyroptosis is also closely involved in cancers that develop as a result of inflammation, such as liver cancer, esophageal cancer, pancreatic cancer, and colon cancer. Here, we review the function and mechanism of pyroptosis in inflammatory disease development and provide a comprehensive description of the potential role of pyroptosis in inflammatory diseases.

Peptidase domain containing associated with muscle regeneration 1 (PAMR1) is frequently lost in breast cancer samples and is considered as a tumor suppressor. The roles and mechanisms of PAMR1 in other types of cancers are still unclear. In our present study, we identified PAMR1 as an invasion-related regulator in cervical cancer. Public database and immunohistochemical (IHC) analysis showed that the expression level of PAMR1 in cervical cancer tissues was lower than that in normal cervix tissues and was negatively related to clinicopathologic features. The high expression of PAMR1 also predicted a better prognosis of cervical cancer patients. CCK8, Transwell, and wound-healing assays demonstrated that knockdown of PAMR1 facilitated the proliferation, migration, and invasion of cervical cancer cells. Additionally, gene set enrichment analysis (GSEA) showed a variety of cancer-related pathways potentially activated or suppressed by PAMR1. Moreover, we verified that PAMR1 inhibited MYC target and mTORC1 signaling pathways. In conclusion, our study revealed the suppressor role of PAMR1 in cervical cancer, providing a new insight into the molecular mechanism of cervical cancer progression.

Predictive models could indicate the clinical outcome of patients with carcinoma. Cervical cancer is one of the most frequently diagnosed female malignancies. Herein, we proposed an immune infiltration-related gene signature that predicts prognosis of patients with cervical cancer and depicts the immune landscape as well. We utilized the transcriptome data of The Cancer Genome Atlas (TCGA) and estimated the infiltration level of 28 immune cell types. We screened out four immune cell types conducive to patient survival and recognized their shared differentially expressed genes (DEGs). Four core genes (CHIT1, GTSF1L, PLA2G2D, and GNG8) that composed the ultimate signature were identified via univariate and multivariate Cox regression. The optimal model we built up could distinguish patients with cervical cancer into high-score and low-score subgroups. These two subgroups showed disparity in aspects of patient survival, immune infiltration landscape, and response to immune checkpoint inhibitors. Additionally, we found that GTSF1L was decreased gradually along with the severity of cervical lesions, and its potential role in immune contexture and clinical practice were also demonstrated. Our results suggested that the Immunoscore based on four immune-related genes could serve as a supplementary criterion to effectively foresee the survival outcome, tumor infiltration status, and immunotherapy efficacy of cervical cancer patients.

RNA sensors detect foreign and endogenous RNAs to protect the host by initiating innate and adaptive immune response. In tumor microenvironment (TME), activation of RNA sensors induces tumor-inhibitory cytotoxic T lymphocyte responses and inhibits the activity of immunosuppressive cells though stimulating type I IFN signaling pathway. These characteristics allow RNA sensors to be prospective targets in tumor immunotherapy. Therefore, a comprehensive understanding of the roles of RNA sensors in TME could provide new insight into the antitumor immunotherapy. Moreover, RNA sensors could be prominent triggering targets to synergize with immunotherapies. In this review, we highlight the diverse mechanisms of RNA sensors in cancer immunity and their emerging contributions in cancer immunotherapy, including monotherapy with RNA sensor agonists, as well as combination with chemotherapy, radiotherapy, immune checkpoint blockade or cancer vaccine.

Aim: To uncover a novel lncRNA–miRNA–mRNA network associated with high-grade serous ovarian cancer metastasis. Material & methods: The candidate differentially expressed lncRNAs were obtained from RNA-sequencing data and determined by functional experiments. The downstream miRNAs and mRNAs were identified by bioinformatic prediction and subjected to functional enrichment analysis. Results: The expression levels of lncRNA ENTPD1-AS1/PRANCR/NR2F2-AS1 were reduced in omental metastatic tissues. Similar differential expression patterns of these lncRNAs were also found in lnCAR database and we verified their tumor suppressive roles by performing functional experiments. Furthermore, we predicted miRNAs and mRNAs via bioinformatic tools and validated their alteration in expression levels in presence of lncRNA interference. Conclusion: We proposed a potential ceRNA regulatory mechanism in high-grade serous ovarian cancer omental metastasis

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