Alteration of microRNA profiles by a novel inhibitor of human La protein in HBV‐transformed human hepatoma cells

Pan, Jiaqian; Tong, Shuangmei; Tang, Jing

doi:10.1002/jmv.24941

Cited by 4 publications

(3 citation statements)

References 46 publications

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“…Recently, we used microarray and quantitative real‐time PCR to investigate the mechanism of H11‐mediated inhibition of HBV infection. The results showed that HBSC11‐induced inhibition of HBV replication was mediated via miR‐ 3912‐5p, miR‐6793‐5p, and miR‐7159‐5p and participation in the Wnt, beta‐catenin, and PPAR signaling pathways . Further research is underway on this subject.…”

Section: Discussionmentioning

confidence: 94%

Study on the structure optimization and anti‐hepatitis B virus activity of novel human La protein inhibitor HBSC11

Tong

Pan

Tang

2019

Journal of Medical Virology

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In our previous study, Methyl pyrazolo[1,5‐a] pyridine‐2‐carboxylate (HBSC11) was shown to combine with La protein, which conferred anti‐hepatitis B virus (HBV) effects. The purpose of this study was to optimize, synthesize, and evaluate the anti‐HBV activity of HBSC11. The methyl group of HBSC11 was substituted with hydrophobic, hydrophilic, and tricyclic groups to generate novel HBV inhibitors with desirable potency. On in vitro evaluation, several derivatives exhibited good anti‐HBV activity compared with control. In particular, compound 5a reduced the level of HBV antigen by approximately 50%, which was similar to the activity of entecavir. In a mouse model, 5a showed 98.9% inhibition rate for HBV DNA, 57.4% for HBsAg, and 46.4% for HBeAg; the corresponding rates in the control group were 90.8, 3.8, and 9.8%, respectively. In addition, prediction of binding modes and physicochemical properties showed that 5a formed hydrogen bonds with La protein and conformed well to the Lipinski's rule of five. Our results suggest that 5a is a potential new anti‐HBV drug.

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Section: Discussionmentioning

confidence: 94%

Study on the structure optimization and anti‐hepatitis B virus activity of novel human La protein inhibitor HBSC11

Tong

Pan

Tang

2019

Journal of Medical Virology

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“…La protein functions as an RNA chaperone and advances the synthesis of tRNA by processing the pre-tRNA precursor's 5-and 3-prime terminals. La protein interacts with particular RNA molecule types to control how they are processed downstream, stop them from misfolding, and promote proper transcript folding and maturation [25,26]. La protein also participates in the mRNAs' internal ribosome entry site (IRES)-mediated translation pathway [27].…”

Section: Introductionmentioning

confidence: 99%

Compounds from Morchella esculenta as Potential Inhibitors of RNA-Binding Protein La in Ovarian Cancer: A Molecular Modeling and Quantum Mechanics Approach

Dairo,

Ward,

Soendergaard

et al. 2023

Preprint

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Ovarian cancer (OC) is implicated in most gynecological cancer-related deaths. Currently, the primary treatments for OC are surgery and chemotherapy using platinum-based drugs to induce remission. However, OC recurs in 70-80% of patients within two years, which usually results in the death of most OC patients. La protein is significantly expressed in various malignant tumors, including OC. Previous studies reported that OC patients have significantly higher levels of La protein expression in their serum than healthy individuals, which is related to the poor response to platinum-based chemotherapy. Inhibiting La protein could control the expression of the potential downstream genes involved in promoting proliferation and chemotherapy resistance to OC, which could serve as a therapeutic intervention in treating OC. Extract from Morchella esculenta (morel mushroom) has been reported to contain anti-cancer properties, but no study has reported the interaction of its bioactive compounds with La protein in OC. This study examines the interaction of La protein with some bioactive compounds of Morchella esculenta, as well as their pharmacokinetics and thermochemical properties using structural bioinformatics and advanced theoretical chemistry techniques. Molecular modeling techniques incorporating molecular docking, free energy calculation, MD simulation, drug-likeness, and quantum chemical calculations, including the global hybrid and long-range corrected density functional theory approximations, were employed in this study. Thus, the results identify hits compounds from morchella esculanta, which could serve as a starting for the development of novel LA protein inhibitors for OC therapeutics.

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“…It combines with specific RNA molecules to regulate its downstream processing. La protein promotes the correct folding of transcripts, prevents the misfolding, and promotes the maturation of transcripts ( 6 , 7 ). It also participates in the internal ribosome entry site (IRES)-mediated translation of mRNA ( 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

La protein regulates protein expression by binding with the mRNAs of target genes and participates the pathological process of ovarian cancer

Huang

Zhu

et al. 2022

Front. Oncol.

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Research on the mechanism and new targets of ovarian cancer is of great significance to reduce the high mortality and drug resistance of ovarian cancer. Human La protein has been found to be highly expressed in a variety of malignant tumors and plays a role in tumorigenesis and development through its RNA-binding function. However, its role and mechanism in ovarian cancer are not completely clear. The present study showed that La protein was highly expressed in serum and tissues of patients with ovarian cancer by ELISA and immunohistochemistry, and the high expression of La protein was associated with the increased degree of malignancy and poor prognosis by searching the KM plotter database. Interference of the La gene resulted in a significant decrease in the proliferation, migration, and invasion of ovarian cancer cells with growth block in the G1 phase and increasing apoptosis. By RNA binding protein immunoprecipitation, transcriptome sequencing, and proteomics, 14 downstream target genes were screened. The La protein might affect the protein expression of these 14 genes by binding with the mRNAs. Therefore, it played a role in the pathological process of ovarian cancer.

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Alteration of microRNA profiles by a novel inhibitor of human La protein in HBV‐transformed human hepatoma cells

Cited by 4 publications

References 46 publications

Study on the structure optimization and anti‐hepatitis B virus activity of novel human La protein inhibitor HBSC11

Study on the structure optimization and anti‐hepatitis B virus activity of novel human La protein inhibitor HBSC11

Compounds from Morchella esculenta as Potential Inhibitors of RNA-Binding Protein La in Ovarian Cancer: A Molecular Modeling and Quantum Mechanics Approach

La protein regulates protein expression by binding with the mRNAs of target genes and participates the pathological process of ovarian cancer

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