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This experiment investigates how the miR-99b/let-7e/miR-125a cluster regulates the mechanism of NR6A1 involved in the invasive and metastatic effects of pancreatic cancer (PCa). Bioinformatics prediction and dual luciferase reporter gene assay were applied to verify the targeted relationship between miR-99b/let-7e/miR-125a and NR6A1. ASPC1 cells underwent transfection with lentiviruses to overexpress miR-99b/let-7e/miR-125a (individual or together) to explore functions of miR-99b/let-7e/miR-125a cluster governing NR6A1 in PCa. The detection of tumorigenesis was verified by tumor formation assay in nude mice in vivo, and mouse models of liver metastasis of PCa observed cell metastasis of PCa. MiR-99b/let-7e/miR-125a cluster was screened for differential expression in PCa. NR6A1 was confirmed as a target gene of the miR-99b/let-7e/miR-125a cluster. Findings demonstrated that overexpression of the miR-99b/let-7e/miR-125a cluster inhibited cell invasion, metastasis, proliferation, and tumorigenesis in PCa. Conversely, overexpressed NR6A1, a crucial gene in the miR-99b/let-7e/miR-125a cluster, promoted cell invasion, migration, and proliferation in PCa. Moreover, the overexpression of the miR-99b/let-7e/miR-125a cluster inhibited liver metastases and tumor formation. Thus, the study concludes that the miR-99b/let-7e/miR-125a cluster impedes the invasion and metastasis of PCa cells via targeting the NR6A1 gene., Competing Interests: None., (AJCR Copyright © 2024.)

Objective: The aim of this investigation was to explore the correlation between the levels of tumor-infiltrating CD8 + and CD4 + T cells and the quantitative pharmacokinetic parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced gastric cancer. Methods: We retrospectively analyzed the data of 103 patients with histopathologically confirmed advanced gastric cancer (AGC). Three pharmacokinetic parameters, K ep , K trans , and V e , and their radiomics characteristics were obtained by Omni Kinetics software. Immunohistochemical staining was used to determine CD4 + and CD8 + TILs. Statistical analysis was subsequently performed to assess the correlation between radiomics characteristics and CD4 + and CD8 + TIL density. Results: All patients included in this study were finally divided into either a CD8 + TILs low-density group ( n = 51) (CD8 + TILs < 138) or a high-density group ( n = 52) (CD8 + TILs ≥ 138), and a CD4 + TILs low-density group ( n = 51) (CD4 + TILs < 87) or a high-density group ( n = 52) (CD4 + TILs ≥ 87). ClusterShade and Skewness based on K ep and Skewness based on K trans both showed moderate negative correlation with CD8 + TIL levels ( r = 0.630-0.349, p < 0.001), with ClusterShade based on K ep having the highest negative correlation ( r = -0.630, p < 0.001). Inertia-based K ep showed a moderate positive correlation with the CD4 + TIL level ( r = 0.549, p < 0.001), and the Correlation based on K ep showed a moderate negative correlation with the CD4 + TIL level, which also had the highest correlation coefficient ( r = -0.616, p < 0.001). The diagnostic efficacy of the above features was assessed by ROC curves. For CD8 + TILs, ClusterShade of K ep had the highest mean area under the curve (AUC) (0.863). For CD4 + TILs, the Correlation of K ep had the highest mean AUC (0.856). Conclusion: The radiomics features of DCE-MRI are associated with the expression of tumor-infiltrating CD8 + and CD4 + T cells in AGC, which have the potential to noninvasively evaluate the expression of CD8 + and CD4 + TILs in AGC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Li, Xia, Zhao, Wang, Jin, Liu, Yang, Shen and Lu.)