Background: The global burden and trends in gynecological cancer (GC) by menopausal status worldwide remain unclear. Methods: Data on the number of incident cases and deaths, as well as age-standardized rates (ASR) and risk factors for GC in pre- and post-menopausal women were obtained from the Global Burden of Disease (GBD) Study 2019. The estimated annual percent change was calculated to quantify the temporal trend of GC burden by menopausal status between 1990 and 2019. The Bayesian age-period-cohort model was used to predict the trends in age-standardized incidence and mortality rates for pre- and post-menopausal GC during 2020–2040. Results: In 2019, an estimated 400 146 pre-menopausal and 879 476 post-menopausal GC cases were newly diagnosed worldwide, with ~111 420 and 442 821 GC-related deaths occurring in each menopausal group, respectively. The majority of both pre- and post-menopausal GC cases in low-to-middle-SDI regions was due to cervical cancer. In high- and high-middle-SDI regions, pre-menopausal GC was primarily attributed to cervical cancer, while post-menopausal GC was mainly attributed to uterine cancer. Additionally, the contribution of uterine cancer to GC was higher among post-menopausal women than pre-menopausal women, across all SDI levels and geographical regions. ASIRs either remained stable or increased from 1990 to 2019 worldwide for both pre- and post-menopausal GC [an average change of 0.03% (95% CI –0.02 to 0.08) and 0.09% (0.05–0.13) per year, respectively]. However, the age-standardized mortality rates (ASMRs) declined by an annual average of 0.86% (95% CI –0.92 to –0.8) and 0.63% (95% CI –0.66 to –0.6) globally during the same period. The risk-attributable proportion of post-menopausal GC deaths was higher than that of pre-menopausal GC and increased with increasing SDI. The projections indicate an increasing trend in the burden of pre-menopausal GC from 2020 to 2040, while the burden of post-menopausal GC is expected to decline. Conclusions: GC continues to be a significant public health concern worldwide, with notable regional and demographic disparities in the burden based on menopausal status. Policymakers and healthcare providers must be proactively aware of these evolving trends and tailor age-appropriate and region-specific screening strategies, as well as allocate resources accordingly.

A lipid droplet (LD) is an organelle that consists of a phospholipid monolayer and a neutral lipid core, with proteins embedded in or attached to its surface. Until recently, cancers had long been regarded as genetic disorders with the abnormal activation of oncogenes and inactivation of tumor suppressor genes before their quality of a metabolic disorder began to be recognized. The last decade has witnessed the recognition of several metabolic characteristics of cancer cells, among which one is the accumulation of lipid droplets; therefore, attention has been given to exploring the role of LDs in carcinomas. In addition, there has been a remarkable expansion in understanding the complexity of LD's function in cellular homeostasis, including but not limited to energy supply, endoplasmic reticulum (ER) stress and oxidative stress management, or lipotoxicity alleviation. Thus, lipid droplet-associated proteins, which to a great extent determine the dynamics of a lipid droplet, have attracted the interest of numerous cancer researchers and their potential as cancer diagnostic biomarkers and therapeutic targets has been affirmed by emerging evidence. In this review, we systematically summarize the critical role of LDs in cancer and then focus on four categories of lipid droplet-associated proteins having the most direct influence on LD biosynthesis (diacylglycerol acyltransferase 1 (DGAT1) and diacylglycerol acyltransferase 2 (DGAT2)), degradation (adipose triglyceride lipase (ATGL)), and two renowned protein families on the LD surface (perilipins and cell death-inducing DNA fragmentation factor alpha-like effectors (CIDEs)). In this way, we aim to highlight their important role in tumor progression and their potential in clinical applications.

7-methylguanosine (m⁷G) modification is recently found to conservatively exist in RNA internal position besides mRNA caps and mediates the various RNA metabolisms. As the core confirmed transmethylase of m⁷G modification, METTL1 has been reported in certain human cancers. However, the role of internal m⁷G at miRNAs and its core writer METTL1 in bladder cancer (BCa) remains to be elucidated. Here, we demonstrated that METTL1 was indispensable for BCa proliferation and metastasis in vitro and in vivo. By combining miRNA sequencing, m⁷G methylated RNA immunoprecipitation (MeRIP) and RIP, we identified METTL1 promoted the processing of miR-760 in an m⁷G-dependent manner. Transcription sequencing suggested that METTL1 indirectly degrades tumor suppressor ATF3 mRNA mediated by miR-760. Together, we concluded a regulatory axis composed of METTL1/m⁷G/miR-760/ATF3 in regulating BCa progression and provided potential therapeutic targets for BCa.

Aberrant expression of the zinc finger protein (ZIC) family has been extensively reported to contribute to progression and metastasis in multiple human cancers. However, the functional roles and underlying mechanisms of ZIC2 in non-small cell lung cancer (NSCLC) are largely unknown. In this study, ZIC2 expression was evaluated using qRT-PCR, western blot, and immunohistochemistry, respectively. Animal experiments in vivo and functional assays in vitro were performed to investigate the role of ZIC2 in NSCLC. Luciferase assays and chromatin immunoprecipitation (ChIP) were carried out to explore the underlying target involved in the roles of ZIC2 in NSCLC. Here, we reported that ZIC2 was upregulated in NSCLC tissues, and high expression of ZIC2 predicted worse overall and progression-free survival of NSCLC patients. Silencing ZIC2 repressed tumorigenesis and reduced the anoikis resistance of NSCLC cells. Mechanical investigation further revealed that silencing ZIC2 transcriptionally inhibited Src expression and inactivated steroid receptor coactivator/focal adhesion kinase signaling, which further attenuated the anoikis resistance of NSCLC cells. Importantly, our results showed that the number of circulating tumor cells (CTCs) was positively correlated with ZIC2 expression in NSCLC patients. Collectively, our findings unravel a novel mechanism implicating ZIC2 in NSCLC, which will facilitate the development of anti-tumor strategies in NSCLC.

Breast cancer stands as the most prevalent cancer diagnosed worldwide, often leading to brain metastasis, a challenging complication characterized by high mortality rates and a grim prognosis. Understanding the intricate mechanisms governing breast cancer brain metastasis (BCBM) remains an ongoing challenge. The unique microenvironment in the brain fosters an ideal setting for the colonization of breast cancer cells. The tumor microenvironment (TME) in brain metastases plays a pivotal role in the initiation and progression of BCBM, shaping the landscape for targeted therapeutic interventions. Current research primarily concentrates on unraveling the complexities of the TME in BCBM, with a particular emphasis on neuroglia and immune cells, such as microglia, monocyte-derived macrophages (MDMs), astrocytes and T cells. This comprehensive review delves deeply into these elements within the TME of BCBM, shedding light on their interplay, mechanisms, and potential as therapeutic targets to combat BCBM.