TOPK Inhibition Enhances the Sensitivity of Colorectal Cancer Cells to Radiotherapy by Reducing the DNA Damage Response.

OBJECTIVE: Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistance in lung cancer. However, the role of TOPK inhibition in enhancing radiosensitivity of colorectal cancer (CRC) cells is unclear. This study aimed to evaluate the radiosensitization of TOPK knockdown in CRC cells. METHODS: The expression of TOPK was detected in CRC tissues by immunohistochemistry, and the effect of TOPK knockdown was detected in CRC cells by Western blotting. CCK-8 and clonogenic assays were used to detect the growth and clonogenic ability of CRC cells after TOPK knockdown combined with radiotherapy in CRC cells. Furthermore, proteomic analysis showed that the phosphorylation of TOPK downstream proteins changed after radiotherapy. DNA damage was detected by the comet assay. Changes in the DNA damage response signaling pathway were analyzed by Western blotting, and apoptosis was detected by flow cytometry. RESULTS: The expression of TOPK was significantly greater in CRC tissues at grades 2-4 than in those at grade 1. After irradiation, CRC cells with genetically silenced TOPK had shorter comet tails and reduced expression levels of DNA damage response-associated proteins, including phospho-cyclin-dependent kinase 1 (p-CDK1), phospho-ataxia telangiectasia-mutated (p-ATM), poly ADP-ribose polymerase (PARP), and meiotic recombination 11 homolog 1 (MRE11). CONCLUSIONS: TOPK was overexpressed in patients with moderately to poorly differentiated CRC. Moreover, TOPK knockdown significantly enhanced the radiosensitivity of CRC cells by reducing the DNA damage response.

Dietary Shifts in the Adaptation to Changing Marine Resources: Insights from a Decadal Study on Greater Lizardfish (Saurida tumbil) in the Beibu Gulf, South China Sea.

Understanding dietary behavior during the individual development of marine predators and its temporal variations elucidates how species adapt to changes in marine resources. This is crucial for predicting marine predators' habitat selection and the natural population's responses to environmental changes. The authors conducted a comparative analysis of dietary shift strategies and trophic level variations in Greater lizardfish (Saurida tumbil) in the Beibu Gulf during two distinct periods (2010 and 2020) using stomach content and stable isotope analysis methods. Possible driving factors for these changes were also explored. Changes in the fishery community structure and the decline in the abundance of primary prey resources have led the S. tumbil population to diversify their prey species, utilize alternative resources, and expand their foraging space. However, the species' foraging strategy, characterized by chasing and preying on schooling and pelagic prey, promoted stability in their feeding behavior across spatial and temporal scales. The main prey items remained demersal and pelagic fish species, followed by cephalopods and crustaceans. Similar to other generalist fish species, ontogenetic dietary shifts (ODSs) indicated a partial transition towards larger prey items. However, the timing and magnitude of the ODSs varied between the two periods, reflecting life-history variations and adaptive adjustments to environmental changes. In comparison to 2010, the population's mean body length (BL) increased in 2020, and the proportion of the population feeding on pelagic-neritic prey significantly increased. However, the δ15N values were lower, indicating that the shift in the ecological niche of preferred prey from demersal to pelagic-neritic was the primary cause of the decrease in trophic levels. In the future, we will conduct further quantitative research integrating the spatiotemporal data of both predators and prey to clarify the relationships between marine predators' feeding behavior, trophic levels, and changes in prey community structure.

The Sympatric Coexistence Mechanism: A Case Study of Two Penahia Species in the Beibu Gulf, South China Sea.

The study of trophic relationships among closely related species plays an important role in deepening our understanding of the resource utilization characteristics, differentiation patterns, and population dynamics of co-occurring species in the same habitat. This research uses two congeneric fish species, Pennahia pawak and Pennahia anea, as examples. Based on a stomach content analysis and a carbon-nitrogen stable isotope analysis, a comparative analysis of their feeding habits and trophic niches is conducted. Additionally, a spatial niche analysis is employed to explore the coexistence and competitive mechanisms between these two closely related fish species. The results show that specialized feeding habits mitigate intraspecific competition as the population densities increase. The carbon and nitrogen stable isotope analysis reveals variations in the feeding habits and trophic levels with body length, indicating adaptive shifts in prey selection. Despite similar food resources, niche differentiation arises due to differences in dominant prey, facilitating coexistence. Differences in spatial niche further contribute to niche separation and coexistence. In resource-limited environments, species such as Pennahia utilize trophic and spatial niche differentiation to collectively exploit resources and achieve coexistence, with implications for fishery management favoring Pennahia resource occupancy capabilities.