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Yuanyuan Chen

Publications and source records attributed to Yuanyuan Chen.

3 recordsLinked to original sources
PubMed2026

Hypoxia-inducible factor-1α promotes the malignant progression of cervical cancer cells by regulating lactate dehydrogenase A-mediated glycolysis.

BACKGROUND: Enhanced glycolysis is a hallmark of metabolic reprogramming in cervical cancer and plays a key role in tumor progression. Hypoxia-inducible factor-1α (HIF-1α), a core regulator of glycolytic metabolism, remains incompletely characterized in cervical cancer. This study aimed to investigate the expression pattern and clinical significance of HIF-1α in cervical cancer, and to explore its association with malignant biological behavior and lactate dehydrogenase A (LDHA)-related glycolytic metabolism in cervical cancer cells. METHODS: The expression level, clinicopathological features, immune infiltration correlation, and prognostic value of HIF-1α in cervical cancer were analyzed based on the The Cancer Genome Atlas (TCGA) database. HIF-1α overexpression and knockdown models were established in HeLa and Caski cells. Cell viability and invasive ability were assessed by Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect changes in LDHA expression. Lactate production was measured using a lactate assay kit, and intracellular reactive oxygen species (ROS) levels were determined by flow cytometry. RESULTS: Bioinformatics analysis showed that HIF-1α was highly expressed in cervical cancer and was closely associated with patient age, menopausal status, immune cell infiltration, and poor prognosis. Kaplan-Meier survival analysis demonstrated that patients with high HIF-1α expression had significantly worse overall survival (OS) than those with low expression. In vitro functional experiments further confirmed that HIF-1α overexpression significantly enhanced the viability and invasive ability of HeLa and Caski cells, whereas HIF-1α knockdown produced the opposite effects. HIF-1α overexpression was associated with increased messenger RNA (mRNA) and protein expression levels of LDHA, a key glycolytic molecule, along with increased lactate production and elevated intracellular ROS levels. CONCLUSIONS: HIF-1α is aberrantly highly expressed in cervical cancer and may enhance glycolytic activity by upregulating LDHA expression, thereby promoting the proliferation and invasion of cervical cancer cells. These findings suggest that HIF-1α could serve as a potential diagnostic, prognostic, and therapeutic target biomarker for cervical cancer.

Hypoxia-inducible factor-1α (HIF-1α)↗
PubMed2026

Proinsulin regulators identified with CRISPR screen and in vivo mouse QTL mapping.

Altered proinsulin levels in β-cells and bloodstream are hallmarks of diabetes and other diseases, but our knowledge about the proinsulin regulators remains limited. Here we perform a genome-wide CRISPR screen to identify 84 proinsulin regulators that alter intracellular proinsulin/insulin ratio in a mouse β-cell line. The proinsulin regulators are distinct from the insulin regulators from a previous orthogonal CRISPR screen. Functional annotation of the proinsulin regulators highlights Golgi as the primary organelle for proinsulin storage and regulation. Trafficking towards the Golgi increases the intra-cellular proinsulin/insulin ratio, while trafficking away from the Golgi, including exocytosis and Golgi-to-ER retrograde transport, decreases the intracellular proinsulin levels. We also map mouse quantitative trait loci (QTLs) associated with plasma proinsulin levels and use the CRISPR screen results to pinpoint the causal genes within the QTL loci. Interestingly, protein disulfide isomerase Pdia6 is the strongest hit from both CRISPR screen and the in vivo QTL mapping. Knocking down Pdia6 significantly reduce proinsulin accumulation in Golgi and secretory granules. Intriguingly, Pdia6-depletion in both human and mouse β-cells does not affect the folding status of proinsulin but causes significantly impaired proinsulin production through a UPR-independent mechanism. Taken together, our genetic profiles provide mechanistic insights into the regulation of proinsulin/insulin homeostasis.

Animals↗
PubMed2025

Genomic resequencing unravels species differentiation and polyploid origins in the aquatic plant genus Trapa.

Trapa L. is a non-cereal aquatic crop with significant economic and ecological value. However, debates over its classification have caused uncertainties in species differentiation and the mechanisms of polyploid speciation. This study employed whole-genome resequencing together with the fruit morphology of 229 Trapa accessions (153 Asian and 76 North American samples) to elucidate species differentiation and polyploidization events in Trapa. For the species with AA genome and large fruits, clear genetic differentiation was found between two clades with different geographic origins, that is, from the Yangtze River and Amur River basins. The invasive AA species in North America (T. natans) was identified as originating from the Amur River based on genetic and morphological similarities, while all the cultivated accessions were AA species originating from the Yangtze River with severe genetic impoverishment. The separation of the two BB species with small seeds, that is, T. incisa and T. maximowiczii, was strongly supported by both morphological and genetic evidence. For the tetraploids, Asian and North American tetraploids were revealed to have distinct evolutionary origins. Asian allotetraploids (AABB) originated through hybridization between AA diploids from the Yangtze River Basin and BB diploids T. maximowiczii, supported by nuclear and chloroplast evidence. In contrast, the invasive North American tetraploids (T. bispinosa var. iinumai) exhibited an AACC-like genome, suggesting an independent polyploidization involving an unknown "CC" diploid. These findings provide critical insights into Trapa's complex evolutionary history, polyploidizations, and invasive origins, offering a genomic foundation for the conservation and sustainable utilization of the underutilized aquatic crop amid global environmental challenges.

Polyploidy↗