Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026010
Persicaria chinensis, a well-known traditional Chinese medicinal herb that is both edible and medicinal, has been widely acknowledged for its therapeutic effects, such as anti-inflammatory, antioxidant, and antitumor activities. However, the role of miRNAs from this plant in the cross-kingdom regulation of human diseases has not been investigated. In this study, we analyze the miRNA expression profile of P. chinensis using high-throughput sequencing and identify a total of 673 miRNAs, including 422 novel miRNAs that are unique to this plant and 251 conserved miRNAs. Among the conserved miRNAs, pch-miR319a is found to be the most abundant. Moreover, food-oriented pch-miR319a accumulates in the uterus and tumors and exhibits a rich repertoire of target genes within cancer-related pathways, demonstrating significant cross-kingdom regulatory potential. Utilizing the dual-luciferase reporter gene assay, we demonstrate that pch-miR319a from P. chinensis targets the Itga3 gene, which is associated with cervical cancer progression. Overexpression of pch-miR319a significantly decreases the viability, migration, and induces apoptosis of HeLa cervical cancer cells in vitro. Moreover, in a syngeneic mouse tumor model of cervical cancer, treatment with pch-miR319a effectively inhibits tumor growth and downregulates the expressions of ITGA3 and the proliferation marker Ki-67. Our study highlights the potential of pch-miR319a from P. chinensis as a novel therapeutic agent for cervical cancer by targeting ITGA3 and provides new insights into the cross-kingdom regulatory mechanisms of plant miRNAs in human diseases.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025145
Angiopoietin-like 4 (ANGPTL4) expression is increased in wound tissue and contributes to wound healing. However, the underlying mechanisms are not fully understood. Here, we demonstrate that ANGPTL4 expression is significantly increased in epidermal stem cells (EpSCs) in the periwound epidermis during wound healing in mice. Increased Angptl4 expression is positively correlated with increased expressions of tumor growth factor-α, interleukin-1β, epidermal growth factor, nerve growth factor, fibroblast growth factor 7, and transforming growth factor-β1. Each of these molecules induces Angptl4 expression in mouse EpSCs. RNA sequencing of EpSCs derived from wild-type and Angptl4 knockout (Angptl4–/–) mice reveals altered expressions of genes involved in the cell cycle and cell proliferation in Angptl4–/– EpSCs, including a decrease in cyclin E2/A2/B1 and cyclin-dependent kinase 1 (Cdk1) expression; an increase in Cdk inhibitor 2a (Cdkn2a) and Cdkn2b expression; and a decrease in the prolactin (PRL) family members Prl2a1, Prl8a1, Prl8a9, and Prl8a6. Mechanistic studies reveal that ANGPTL4 stimulates EpSC proliferation via PRL8a6-mediated upregulation of cyclins A2/E2/B1 and Cdk1, downregulation of Cdkn2a, and acceleration of cell cycle progression from the G1 to the S and G2 phases. In vivo studies demonstrate that Prl8a6 mRNA is upregulated by ANGPTL4 in mouse periwound tissue during skin wound healing. Knockdown of Angptl4 or Prl8a6 in periwound skin tissue impairs EpSC proliferation and delays wound re-epithelialization. In conclusion, our study demonstrates that, after skin injury, elevated levels of proinflammatory cytokines and growth factors in periwound tissue stimulate Angptl4 expression in EpSCs and that ANGPTL4 promotes EpSC proliferation by increasing Prl8a6 expression, thereby accelerating wound re-epithelialization.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025170
Cryptococcus gattii causes cryptococcosis and life-threatening cryptococcal meningitis. Currently, the pathogenic virulence mechanisms of C. gattii remain a significant area of ongoing research with considerable unexplored aspects. On the basis of our established research, a sub-cluster of strains with independent evolutionary relationships from WM276 in the phylogenetic analysis of VGI-type strains is identified. In vivo infection experiments on this sub-branch of strains reveal that there are hypervirulent strains and hypovirulent strains among these strains, and the virulence differences are significant (P < 0.001). Bioinformatic interrogation of differentially expressed genes reveals that the catalase-encoding gene CGB_J0620W, CAT2, is a pivotal virulence-associated gene. The hypervirulent clinical isolate G4 (G4-WT) is selected as the parental strain, from which an isogenic CAT2-knockout mutant (cat2Δ) is constructed via homologous recombination, which shows increased sensitivity to oxidative stress, as well as growth defects in response to hyperosmosis, 5-fluorocytosine, fluconazole and amphotericin B. The cat2Δ::CAT2 strain exhibits phenotypic restoration to wild type (WT). In the mouse experiments, significant differences in survival (P < 0.001), pulmonary fungal burden (P < 0.01), and alveolar structural damage are observed between the WT and cat2Δ strains, which are completely different from C. neoformans. Moreover, comparative transcriptome analysis is performed on the WT and cat2Δ strains, which reveals that enzymes encoded by CAT2 may be involved in oxidative stress, metabolism and sugar transport. In conclusion, this study may explain the differences in virulence among different genetic evolutionary processes of a sub-cluster of the VGI geneotype of C. gattii and provide a theoretical basis for targeted therapy in a specific genotype population in the future.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026084
Osimertinib is the standard first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring EGFR-sensitive mutations. However, drug resistance inevitably develops, highlighting the critical need for strategies to overcome this resistance and prolong therapeutic efficacy. Understanding the mechanisms underlying drug resistance is essential, and drug-resistant cell models serve as valuable tools for investigating acquired resistance. In this study, we establish an osimertinib resistance evolution model in vitro by continuous high-dose drug induction and identify cell lines exhibiting “permanent” resistance to osimertinib (osimertinib resistant, OR). Transcriptome sequencing (RNA-seq), gain- and loss-of-function assay, including lentiviral-mediated overexpression and RNAi knockdown, pharmacological inhibition, and protein degradation analysis reveal significant alterations in genes associated with epigenetic regulation, notably a marked upregulation of histone deacetylase 6 (HDAC6) in OR cells. Knockdown of HDAC6 or pharmacological inhibition of HDAC6 restores the sensitivity of OR cells to osimertinib, whereas overexpression of HDAC6 in sensitive cells reduces drug efficacy and accelerates the onset of resistance. Furthermore, we find that HDAC6 upregulation promotes EGFR degradation, thereby contributing to resistance. Collectively, our findings demonstrate the utility of drug resistance evolution models in identifying key resistance factors. HDAC6 plays a pivotal role in osimertinib resistance, and targeting HDAC6 may represent a novel therapeutic strategy to overcome resistance and enhance treatment efficacy.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024070
Epidermal stem cells (EpSCs) play a vital role in skin wound healing through re-epithelialization. Identifying chemicals that can promote EpSC proliferation is helpful for treating skin wounds. This study investigates the effect of morroniside on cutaneous wound healing in mice and explores the underlying mechanisms. Application of 10‒50 μg/mL of morroniside to the skin wound promotes wound healing in mice. In vitro studies demonstrate that morroniside stimulates the proliferation of mouse and human EpSCs in a time- and dose-dependent manner. Mechanistic studies reveal that morroniside promotes the proliferation of EpSCs by facilitating the cell cycle transition from the G1 to S phase. Morroniside increases the expression of β-catenin via the glucagon-like peptide-1 receptor (GLP-1R)-mediated PKA, PKA/PI3K/AKT and PKA/ERK signaling pathways, resulting in an increase in cyclin D1 and cyclin E1 expression, either directly or by upregulating c-Myc expression. This process ultimately leads to EpSC proliferation. Administration of morroniside to mouse skin wounds increases the phosphorylation of AKT and ERK, the expressions of β-catenin, c-Myc, cyclin D1, and cyclin E1, as well as the proliferation of EpSCs, in periwound skin tissue, and accelerates wound re-epithelialization. These effects of morroniside are mediated by the GLP-1R. Overall, these results indicate that morroniside promotes skin wound healing by stimulating the proliferation of EpSCs via increasing β-catenin expression and subsequently upregulating c-Myc, cyclin D1, and cyclin E1 expressions through GLP-1R signaling pathways. Morroniside has clinical potential for treating skin wounds.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026010
Persicaria chinensis, a well-known traditional Chinese medicinal herb that is both edible and medicinal, has been widely acknowledged for its therapeutic effects, such as anti-inflammatory, antioxidant, and antitumor activities. However, the role of miRNAs from this plant in the cross-kingdom regulation of human diseases has not been investigated. In this study, we analyze the miRNA expression profile of P. chinensis using high-throughput sequencing and identify a total of 673 miRNAs, including 422 novel miRNAs that are unique to this plant and 251 conserved miRNAs. Among the conserved miRNAs, pch-miR319a is found to be the most abundant. Moreover, food-oriented pch-miR319a accumulates in the uterus and tumors and exhibits a rich repertoire of target genes within cancer-related pathways, demonstrating significant cross-kingdom regulatory potential. Utilizing the dual-luciferase reporter gene assay, we demonstrate that pch-miR319a from P. chinensis targets the Itga3 gene, which is associated with cervical cancer progression. Overexpression of pch-miR319a significantly decreases the viability, migration, and induces apoptosis of HeLa cervical cancer cells in vitro. Moreover, in a syngeneic mouse tumor model of cervical cancer, treatment with pch-miR319a effectively inhibits tumor growth and downregulates the expressions of ITGA3 and the proliferation marker Ki-67. Our study highlights the potential of pch-miR319a from P. chinensis as a novel therapeutic agent for cervical cancer by targeting ITGA3 and provides new insights into the cross-kingdom regulatory mechanisms of plant miRNAs in human diseases.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026084
Osimertinib is the standard first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring EGFR-sensitive mutations. However, drug resistance inevitably develops, highlighting the critical need for strategies to overcome this resistance and prolong therapeutic efficacy. Understanding the mechanisms underlying drug resistance is essential, and drug-resistant cell models serve as valuable tools for investigating acquired resistance. In this study, we establish an osimertinib resistance evolution model in vitro by continuous high-dose drug induction and identify cell lines exhibiting “permanent” resistance to osimertinib (osimertinib resistant, OR). Transcriptome sequencing (RNA-seq), gain- and loss-of-function assay, including lentiviral-mediated overexpression and RNAi knockdown, pharmacological inhibition, and protein degradation analysis reveal significant alterations in genes associated with epigenetic regulation, notably a marked upregulation of histone deacetylase 6 (HDAC6) in OR cells. Knockdown of HDAC6 or pharmacological inhibition of HDAC6 restores the sensitivity of OR cells to osimertinib, whereas overexpression of HDAC6 in sensitive cells reduces drug efficacy and accelerates the onset of resistance. Furthermore, we find that HDAC6 upregulation promotes EGFR degradation, thereby contributing to resistance. Collectively, our findings demonstrate the utility of drug resistance evolution models in identifying key resistance factors. HDAC6 plays a pivotal role in osimertinib resistance, and targeting HDAC6 may represent a novel therapeutic strategy to overcome resistance and enhance treatment efficacy.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025145
Angiopoietin-like 4 (ANGPTL4) is elevated in wound tissue and contributes to wound healing, but the mechanisms remain unclear. This study demonstrates that ANGPTL4 expression is significantly increased in epidermal stem cells (EpSCs) in the periwound epidermis during murine wound healing. Increased Angptl4 expression positively correlates with elevated levels of tumor growth factor-α, interleukin-1β, epidermal growth factor, nerve growth factor, fibroblast growth factor 7, and transforming growth factor-β1, each of which induces Angptl4 in EpSCs. RNA sequencing of EpSCs from wild-type and Angptl4 knockout (Angptl4–/–) mice reveals altered expression of cell cycle and proliferation genes, including decreased cyclin E2/A2/B1 and cyclin-dependent kinase 1 (Cdk1), increased Cdk inhibitor 2a (Cdkn2a) and Cdkn2b, and reduced prolactin (PRL) family members Prl2a1, Prl8a1, Prl8a9, and Prl8a6. Mechanistically, ANGPTL4 stimulates EpSC proliferation via PRL8a6-mediated upregulation of cyclins A2/E2/B1 and Cdk1, downregulation of Cdkn2a, and acceleration of G1 to S and G2 phase progression. In vivo, Prl8a6 mRNA is upregulated by ANGPTL4 in mouse periwound tissue during healing. Knockdown of Angptl4 or Prl8a6 impairs EpSC proliferation and delays re-epithelialization. These findings establish that after skin injury, proinflammatory cytokines and growth factors stimulate Angptl4 in EpSCs, and ANGPTL4 promotes EpSC proliferation by increasing Prl8a6, thereby accelerating wound re-epithelialization.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025057
MEIOB and SPATA22 are gonad-specific proteins essential for meiotic recombination, with mutations linked to oligospermia and azoospermia in human males. The heterodimer recognizes and binds single-stranded DNA (ssDNA) protected by replication protein A (RPA) to promote homologous recombination repair. However, sequence divergence between human and rodent orthologs leads to functional differences. Here, human MEIOB (hMEIOB) and SPATA22 (hSPATA22) were expressed and purified for electrophoretic mobility shift assay (EMSA), magnetic tweezer (MT) assay, and bio-layer interferometry (BLI) to dissect ssDNA binding patterns. hMEIOB alone exhibits low ssDNA-binding affinity and stability, whereas hSPATA22 binds ssDNA faster and more stably, promoting ssDNA condensation. The hMEIOB-hSPATA22 heterodimer displays strong binding affinity and stability. Multiple heterodimers spontaneously aggregate in vitro, with BLI response signals of ~4.31 nm for hSPATA22 alone versus ~19.5 nm for the heterodimer, indicating polymer formation. The hRPA complex weakens the binding affinity of hMEIOB, hSPATA22, and the heterodimer to ssDNA, and binds to hSPATA22 and the heterodimer in vitro, consistent with RPA's role in protecting ssDNA and recruiting repair proteins. This study provides the first single-molecule elucidation of hMEIOB and hSPATA22 binding to ssDNA and verifies their relationship with the RPA complex.