Zheng Wu’s research while affiliated with Shantou University and other places

The sine oculis homeobox homolog (SIX) family, a group of transcription factors characterized by a conserved DNA-binding homology domain, plays a critical role in orchestrating embryonic development and organogenesis across various organisms, including humans. Comprising six distinct members, from SIX1 to SIX6, each member contributes uniquely to the development and differentiation of diverse tissues and organs, underscoring the versatility of the SIX family. Dysregulation or mutations in SIX genes have been implicated in a spectrum of developmental disorders, as well as in tumor initiation and progression, highlighting their pivotal role in maintaining normal developmental trajectories and cellular functions. Efforts to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor development. While the development of inhibitors targeting this gene family is still in its early stages, the significant potential of such interventions holds promise for future therapeutic advances. Therefore, this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers, focusing on its critical role in normal organ development and its implications in gastrointestinal cancers, including gastric, pancreatic, colorectal cancer, and hepatocellular carcinomas. In conclusion, this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis, prognosis, and treatment of gastrointestinal cancers.

Medical education plays a critical role in preparing future doctors, responsible for the well-being and health of individual patients. Given its unique significance, understanding how to enhance the intrinsic motivation of clinical medical undergraduates for a 5-year program is a key research focus in China. Based on this purpose, the transformation of higher education in the major of clinical medicine has been conducted worldwide. To evaluate the attitude of clinical medical undergraduates on the transformation of education, this study investigates the impact of different teaching models on the learning attitudes of students at Shantou University Medical School, aiming to provide insights into effective educational strategies. Within the set-up of different teaching models, involving active-learning classes, English-medium instruction classes, and conventional clinical classes, we employed a comprehensive survey targeting undergraduates enrolled in three distinct teaching models. The survey explored multiple dimensions of learning behaviors, including classroom engagement, study time, and overall motivation. Results indicated that students participating in active learning classes exhibited superior classroom engagement and devoted more time to their studies than those in English-medium instruction classes and conventional clinical classes, while the difference between English-medium instruction classes and conventional clinical classes was not significant. These students reported a higher intrinsic motivation towards their learning experience, suitable to apply self-directed learning methods. In conclusion, this study underscores the importance of adopting diverse and adaptive teaching strategies to cater to the varied learning attitudes of clinical medical undergraduates, suggesting conducting self-evaluation or pre-evaluation of the students for adapting to different clinical teaching methods. Meanwhile, enhancing teacher guidance and support throughout the learning process is essential. By implementing different educational approaches, medical schools can effectively enhance student motivation and educational outcomes, contributing to the advancement of medical education.

Flipped classroom (FC) is considered a student-centered teaching method that improves internal active learning of students and their acquisition of knowledge and skills. Among many medical majors, physiology is quite important as a bridge between basic and clinical principles. However, the complex and abstract nature of physiology causes learning stress to students. As the use of FC is widespread across various majors and principles with beneficial effects, analyzing its application in physiology is important to comprehensively evaluate its effectiveness and advantages, as well as disadvantages, and to improve the specific procedures of FC conduction. This article reviews the research on FC utilization in physiology education and summarizes its effectiveness and feedback from both educators and learners, serving as a guideline to facilitate and promote the development of FC in physiology education.

Background: Recent research suggests that STEAP4, a metalloreductase in vivo, plays a crucial role in various types of tumorigeneses, especially in gastrointestinal cancers. However, few oncogenes have been reported in oral squamous cell carcinoma (OSCC). Therefore, this study aimed to explore the potential role of STEAP4 in OSCC. Methods: The expression level of STEAP4 in OSCC tissues and adjacent normal tissues, was detected using immunohistochemistry. Publicly available online tools were utilized to analyze the expression, prognostic significance, and related enriched pathways of STEAP4 in head and neck squamous cell carcinoma (HNSCC) and OSCC. The relationship between STEAP4 expression and clinicopathological parameters in OSCC patients was validated using the χ2 test and Fisher's exact probability test. Results: STEAP4 exhibited low expression in both HNSCC and OSCC. Whereas the prognosis for HNSCC patients was favorable, OSCC patients had poor outcomes. Genetic variability analysis revealed no alterations in STEAP4 in OSCC, whereas gene amplification was observed in HNSCC, suggesting tumor heterogeneity in STEAP4 among these cancer types. Conclusion: STEAP4, as a risk factor associated with poor patient prognosis, shows tumor heterogeneity in OSCC patients, that is potentially related to genetic mutations or differences in histological distribution of oral mucosa. These findings indicate that STEAP4 could serve as an independent predictor for assessing the prognosis of OSCC patients.

The growing interest in post-translational protein modification, particularly in SUMOylation, is driven by its crucial role in cell cycle regulation. SUMOylation affects various cell cycle regulators, including oncogenes, suggesting its relevance in cancer. SUMO E3 ligases are pivotal in this process, exhibiting diverse functionalities through structural domains and subcellular localizations. A less-explored SUMO E3 ligase, RANBP2, a component of the vertebrate nuclear pore complex, emerges as a central player in cellular cycle processes, as well as in tumorigenesis. The current studies illuminate the importance of RANBP2 and underscore the need for more extensive studies to validate its clinical applicability in neoplastic interventions. Our review elucidates the significance of RANBP2 across various types of malignancies. Additionally, it delves into exploring RANBP2 as a prospective therapeutic target for cancer treatment, offering insights into the avenues that scholars should pursue in their subsequent research endeavors. Thus, further investigation into RANBP2's role in solid tumorigenesis is eagerly awaited.

Breast cancer ranks as the most prevalent cancer globally, surpassing lung cancer, with recurrence/metastasis to be its main account for the cancer-related mortality. MicroRNAs (miRNAs) participate critically in various physiological and pathological processes through posttranscriptional regulation of downstream genes. Our preliminary findings identified miR-338–5p, potentially linked to metastasis in breast cancer, a previously unexplored area. Analysis of the GSE38867 dataset revealed the decreased miR-338–5p expression in metastatic breast cancer compared to normal tissues. Cellular function experiments and a xenograft tumor model demonstrated the inhibitory function of miR-338–5p on the progression of breast cancer in vitro and in vivo. Furthermore, it downregulated the expression of mesenchymal biomarkers and NOTCH1 significantly. With the predicting targets of miR-338–5p and transcription factors of the NOTCH1 gene, coupled with dual luciferase reporter assays, it is identified ETS1 as the interactor between miR-338–5p and NOTCH1. In breast cancer tissues, as well as in our xenograft tumor model, expression of ETS1 and NOTCH1 was positively correlated using immunohistochemical staining. This study reports, for the first time, on the miR-338–5p/ETS1/NOTCH1 axis and its pivotal role in breast cancer proliferation and metastasis. These findings propose a novel therapeutic strategy for breast cancer patients and lays a foundation for its clinical detection and treatment evaluation.

The development of novel drugs from basic science to clinical practice requires several years, much effort, and cost. Drug repurposing can promote the utilization of clinical drugs in cancer therapy. Recent studies have shown the potential effects of lomitapide on treating malignancies, which is currently used for the treatment of familial hypercholesterolemia. We systematically review possible functions and mechanisms of lomitapide as an anti-tumor compound, regarding the aspects of apoptosis, autophagy, and metabolism of tumor cells, to support repurposing lomitapide for the clinical treatment of tumors.

Chronic inflammation is known to increase the risk of gastrointestinal cancers (GICs), the common solid tumors worldwide. Precancerous lesions, such as chronic atrophic inflammation and ulcers, are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis. Unfortunately, due to the lack of effective therapeutic targets, the prognosis of patients with GICs is still unsatisfactory. Interestingly, it is found that six transmembrane epithelial antigens of the prostate (STEAPs), a group of metal reductases, are significantly associated with the progression of malignancies, playing a crucial role in systemic metabolic homeostasis and inflammatory responses. The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress, responding to inflammatory reactions. Under the imbalance status of abnormal oxidative stress, STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process. This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms, with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.

Small nucleolar RNAs (snoRNAs) represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification, thereby contributing significantly to the maintenance of cellular functions related to protein synthesis. SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression, holding immense potential in controlling human diseases. It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types, stages, metastasis, treatment response and/or prognosis in patients. On the other hand, colorectal cancer (CRC), a prevalent malignancy of the digestive system, is characterized by high incidence and mortality rates, ranking as the third most common cancer type. Recent research indicates that snoRNA dysregulation is associated with CRC, as snoRNA expression significantly differs between normal and cancerous conditions. Consequently, assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC. Nevertheless, current comprehension of the potential roles of snoRNAs in CRC remains limited. This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC, providing valuable insights into the discovery of novel biomarkers, therapeutic targets, and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.

Background: NOTCH receptor 3 (NOTCH3) and zinc finger E-box binding protein 1 (ZEB1) play important roles in breast cancer respectively. NOTCH3 maintains the luminal phenotype and inhibits epithelial-mesenchymal transition (EMT) in breast cancer, while ZEB1 and NOTCH3 have the opposite effects. Methods: Public databases were used to predict the expression of NOTCH3 and ZEB1 in breast cancer cell lines. The regulatory effect of NOTCH3 on ZEB1 expression was verified by western blot and RT-PCR. MiRNAs regulating ZEB1 expression were identified by using multiple databases and confirmed by reporter gene experiments. Cellular function experiments were conducted to evaluate the role of NOTCH3/miR-223/ZEB1 in the proliferation and invasion of triple-negative breast cancer (TNBC). Results: NOTCH3 and ZEB1 have opposite expression pattern in MCF-7 cells that over-express LncATB or were incubated in TGF-β to induce EMT. Western blotting and RT-PCR showed that NOTCH3 could regulate expression of ZEB1. MiR-223 inhibited the proliferation and invasion of breast cancer cells via down-regulating the expression of ZEB1. NOTCH3 inhibited the proliferation and invasion of breast cancer cells via up-regulating the expression of miR-223. Clinically, high expression of NOTCH3, miR-223 or low expression of ZEB1 were related to good prognosis of breast cancer patients. Conclusion: The current study reports a novel NOTCH3/miR-223/ZEB1 axis, which can inhibit the proliferation and invasion of breast cancer cells, and may serve as a potential biomarker for the prognosis of breast cancer.