Ferroptosis is a recently discovered essential type of cell death that is mainly characterized by iron overload and lipid peroxidation. Emerging evidence suggests that ferroptosis is a double-edged sword in human cancer. However, the precise underlying molecular mechanisms and their differential roles in tumorigenesis are unclear. Therefore, in this review, we summarize and briefly present the key pathways of ferroptosis, paying special attention to the regulation of ferroptosis as well as its dual role as an oncogenic and as a tumor suppressor event in various human cancers. Moreover, multiple pharmacological ferroptosis activators are summarized, and the prospect of targeting ferroptosis in cancer therapy is further elucidated.

Objective: Esophageal squamous cell carcinoma (ESCC) is one of the most commonly diagnosed cancer types in China. Recent genomic sequencing analysis indicated the over-activation of Hippo/YAP signaling might play important roles for the carcinogenic process and progression for ESCC patients. However, little is known about the molecular mechanisms that controls Hippo signaling activity in ESCC. Our previous studies indicated that PLCE1-an important risk factor for ESCC-linked to ESCC progression through snail signaling, during this period, we found PARK2 was an important downstream target of PLCE1-snail axis. PARK2 was decreased in ESCC human samples, and correlated with good prognosis in ESCC patients. Further research showed that PARK2 could inhibit YAP, which functions as key downstream effectors of the Hippo pathway. Here, we aim to reveal the molecular mechanisms of PARK2 modulated Hippo pathway in ESCC.

The temporal trend of inflammatory bowel disease (IBD) incidence is reported to be increasing in worldwide regions; however, reports focusing on China are sparse. The aim of this study was to provide an overview of the disease burden and clinical features of IBD in the Chinese population. We searched Medline, EMBASE, and another two Chinese databases. A parallel literature review and data extraction were conducted. Meta-analysis was performed to estimate the summary incidence rate of Crohn’s disease (CD) and ulcerative colitis (UC). The constituent ratios with 95% CI were calculated for clinical phenotypes and classifications. The literature review included 47 publications. The summary incidence rate of IBD was 1.74 (95% CI: 1.08; 2.40) per 100,000 person years, and the corresponding incidence rates of CD and UC were 0.40 (95% CI: 0.23; 0.57) and 1.18 (95% CI: 0.81; 1.56) per 100,000 person years, respectively. The sex distribution analysis indicated a male predominance in both CD (sex ratio: 1.64; 95% CI: 1.47–1.84) and UC (sex ratio: 1.29; 95% CI: 1.21–1.38). The clinical characteristics were summarized using data from 2283 CD cases and 17,958 UC cases; in which the majority of CD patients were diagnosed between 17–40 years of age, with non-stricturing and non-penetrating disease, varied disease locations, and less extra-intestinal manifestation. UC cases were featured with later disease diagnosis, a more severe disease course, more segmental lesions, and less extra-intestinal manifestations. Our study provided an estimated disease burden of IBD and demonstrated distinct clinical features in the Chinese population. Large-scale population-based studies are needed to further evaluate these findings.

Deubiquitination is a major form of post-translational protein modification involved in the regulation of protein homeostasis and various cellular processes. Deubiquitinating enzymes (DUBs), comprising about five subfamily members, are key players in deubiquitination. USP10 is a USP-family DUB featuring the classic USP domain, which performs deubiquitination. Emerging evidence has demonstrated that USP10 is a double-edged sword in human cancers. However, the precise molecular mechanisms underlying its different effects in tumorigenesis remain elusive. A possible reason is dependence on the cell context. In this review, we summarize the downstream substrates and upstream regulators of USP10 as well as its dual role as an oncogene and tumor suppressor in various human cancers. Furthermore, we summarize multiple pharmacological USP10 inhibitors, including small-molecule inhibitors, such as spautin-1, and traditional Chinese medicines. Taken together, the development of specific and efficient USP10 inhibitors based on USP10’s oncogenic role and for different cancer types could be a promising therapeutic strategy.

The ENaC/degenerin ion channel superfamily includes the amiloride-sensitive epithelial sodium channel (ENaC) and acid sensitive ionic channel (ASIC). ENaC is a multimeric ion channel formed by heteromultimeric membrane glycoproteins, which participate in a multitude of biological processes by mediating the transport of sodium (Na⁺) across epithelial tissues such as the kidney, lungs, bladder, and gut. Aberrant ENaC functions contribute to several human disease states including pseudohypoaldosteronism, Liddle syndrome, cystic fibrosis, and salt-sensitive hypertension. Increasing evidence suggests that ion channels not only regulate ion homeostasis and electric signaling in excitable cells but also play important roles in cancer cell behaviors such as proliferation, apoptosis, invasion, and migration. Indeed, ENaCs/ASICs had been reported to be associated with cancer characteristics. Given their cell surface localization and pharmacology, pharmacological strategies to target ENaC/ASIC family members may be promising cancer therapeutics.

The epithelial Na⁺ channel/degenerin (ENaC/DEG) superfamily, including the acid-sensing ion channels (ASICs), is characterized by a high degree of similarity in structure but highly diverse in physiological functions. These ion channels have been shown to be important in several physiological functions of normal epithelial cells, including salt homeostasis, fluid transportation and cell mobility. There is increasing evidence suggesting that ENaC/DEG channels are critically engaged in cancer cell biology, such as proliferation, migration, invasion and apoptosis, playing a role in tumor development and progression. In this review, we will discuss recent studies showing the role of ENaC and ASIC channels in epithelial cells and its relationship to the oncogenesis.