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Ning Wu

Publications and source records attributed to Ning Wu.

2 recordsLinked to original sources

miR-2116-5p functions as a tumor suppressor in lung adenocarcinoma by targeting ADAM12 and serves as a prognostic biomarker.

BACKGROUND: MicroRNAs play key roles in tumor progression. miR-2116-5p is downregulated in lung adenocarcinoma (LUAD), and this study investigated its prognostic value and functional role in the disease. MATERIALS AND METHODS: A total of 125 LUAD patients contributed tissue samples. miR-2116-5p and ADAM12 expression in tissues and cell lines were detected by RT&#x2011;qPCR. Clinicopathological correlations of miR-2116-5p were analyzed using the chi-square test. Kaplan&#x2011;Meier and Cox regression were employed to assess prognostic significance. CCK&#x2011;8, Transwell, and dual&#x2011;luciferase reporter assays were performed to investigate miR&#x2011;2116-5p function and its targeting of ADAM12. Rescue experiments validated the functional involvement of ADAM12. RESULTS: Significant downregulation of miR-2116-5p was observed in LUAD tissues and cell lines. Low expression was markedly linked to lymph node metastasis (P&#x2009;=&#x2009;0.013) and advanced TNM stage (P&#x2009;=&#x2009;0.002). Patients exhibiting reduced miR-2116-5p levels showed worse overall survival, and it was identified as an independent prognostic factor (HR&#x2009;=&#x2009;2.521, 95% CI: 1.129-5.628, P&#x2009;=&#x2009;0.020). Functional experiments showed that increasing miR-2116-5p expression suppressed LUAD cell proliferation, migration, and invasion, whereas its knockdown promoted these processes. ADAM12 was confirmed as a direct target, with expression inversely correlated in LUAD tissues (r = -0.749, P&#x2009;<&#x2009;0.001). ADAM12 overexpression effectively counteracted the ability of miR-2116-5p to suppress proliferation, migration, and invasion. CONCLUSION: miR&#x2011;2116-5p suppresses LUAD progression by targeting ADAM12, suggesting it may serve as a prognostic biomarker and therapeutic target.

Humans

Systematic mining and quantification reveal the dominant contribution of non-HLA variations to acute graft-versus-host disease.

Human leukocyte antigen (HLA) disparity between donors and recipients is a key determinant triggering intense alloreactivity, leading to a lethal complication, namely, acute graft-versus-host disease (aGVHD), after allogeneic transplantation. Moreover, aGVHD remains a cause of mortality after HLA-matched allogeneic transplantation. Protocols for HLA-haploidentical hematopoietic cell transplantation (haploHCT) have been established successfully and widely applied, further highlighting the urgency of performing panoramic screening of non-HLA variations correlated with aGVHD. On the basis of our time-consecutive large haploHCT cohort (with a homogenous discovery set and an extended confirmatory set), we first delineated the genetic landscape of 1366 samples to quantitatively model aGVHD risk by assessing the contributions of HLA and non-HLA genes together with clinical factors. In addition to identifying multiple loss-of-function (LoF) risk variations in non-HLA coding genes, our data-driven study revealed that non-HLA genetic variations, independent of HLA disparity, contributed the most to the occurrence of aGVHD. This unexpected major effect was verified in an independent cohort that received HLA-identical sibling HCT. Subsequent functional experiments further revealed the roles of a representative non-HLA LoF gene and LoF gene pair in regulating the alloreactivity of primary human T cells. Our findings highlight the importance of non-HLA genetic risk in the new era of transplantation and propose a new direction to explore the immunogenetic mechanism of alloreactivity and to optimize donor selection strategies for allogeneic transplantation.

Humans