RPL41 sensitizes retinoblastoma cells to chemotherapeutic drugs via ATF4 degradation

Geng, Wen; Ren, Jiaxu; Shi, Huimin; Feng, Qicheng; Xu, Xiaohe; Xiao, Sheng; Jiao, Yisheng; Wang, Aiyuan

doi:10.1002/jcp.30010

Cited by 9 publications

(3 citation statements)

References 42 publications

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“…Recently, activity of human eL41 outside of its ribosomal function was discovered. Human eL41 functioned as a cell-penetrating peptide, interacting with ATF4 and targeting it to the cytoplasmic proteasome for degradation ( 70–72 ). We consider bS22 as a structure-functional homologue of eL41 and therefore investigated if free bS22 also has functions outside the ribosome.…”

Section: Resultsmentioning

confidence: 99%

Sarecycline inhibits protein translation inCutibacterium acnes70S ribosome using a two-site mechanism

Lomakin

Devarkar

Patel

et al. 2023

Nucleic Acids Research

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Acne vulgaris is a chronic disfiguring skin disease affecting ∼1 billion people worldwide, often having persistent negative effects on physical and mental health. The Gram-positive anaerobe, Cutibacterium acnes is implicated in acne pathogenesis and is, therefore, a main target for antibiotic-based acne therapy. We determined a 2.8-Å resolution structure of the 70S ribosome of Cutibacterium acnes by cryogenic electron microscopy and discovered that sarecycline, a narrow-spectrum antibiotic against Cutibacterium acnes, may inhibit two active sites of this bacterium's ribosome in contrast to the one site detected previously on the model ribosome of Thermus thermophilus. Apart from the canonical binding site at the mRNA decoding center, the second binding site for sarecycline exists at the nascent peptide exit tunnel, reminiscent of the macrolides class of antibiotics. The structure also revealed Cutibacterium acnes-specific features of the ribosomal RNA and proteins. Unlike the ribosome of the Gram-negative bacterium Escherichia coli, Cutibacterium acnes ribosome has two additional proteins, bS22 and bL37, which are also present in the ribosomes of Mycobacterium smegmatis and Mycobacterium tuberculosis. We show that bS22 and bL37 have antimicrobial properties and may be involved in maintaining the healthy homeostasis of the human skin microbiome.

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Section: Resultsmentioning

confidence: 99%

Sarecycline inhibits protein translation inCutibacterium acnes70S ribosome using a two-site mechanism

Lomakin

Devarkar

Patel

et al. 2023

Nucleic Acids Research

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“…Construction, culture and transfection of VCR-resistant RB cell line RB cell lines (Y79, WERI-Rb-1, SO-Rb50, and SO-Rb70) were obtained from National Infrastructure of Cell Line Resource (www.cellresource), and human retinal astrocyte (HRA) was purchased from ZQXZ Biotech (Shanghai, China). All the cells were cultured in RPMI-1640 medium (Sigma-Aldrich, Merck KGaA, Darmstadt, Germany) containing 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin-glutamine (100X, Gibco, Grand Island, NY, USA) at 37℃ with 5% CO 2 [21]. The VCR-resistant RB cell line was constructed by E-test, lasting for 9 months, and the concentration of VCR ranged from 75 µg/mL to 600 µg/mL.…”

Section: Clinical Samplementioning

confidence: 99%

Role and mechanism of miR-130a-3p in the chemosensitivity of retinoblastoma cells to vincristine

Tang

et al. 2021

Preprint

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Purpose Chemoresistance remains the primary obstacle threatening the prognosis of retinoblastoma (RB). microRNAs (miRNAs) are acknowledged as critical regulator of drug resistance. This study explored the molecular mechanism of miR-130a-3p affecting the chemosensitivity of RB to vincristine (VCR). Methods miR-130a-3p expression of VCR-sensitive and VCR-resistant RB tissues was detected using RT-qPCR. VCR-resistant RB cell line Y79/VCR was induced. miR-130a-3p expression of Y79/VCR cell line and its corresponding parental cell line was detected. Y79/VCR cells were subjected to miR-130a-3p overexpression treatment. The cell proliferation was measured using MTT assay, and the IC50 value and drug resistance index were examined using CCK-8 assay. The targeting relationship between miR-130a-3p and PAX6 was predicted through bioinformatics analysis and verified using dual-luciferase assay. Functional rescue experiments were conducted to confirm the role of PAX6 in chemosensitivity of RB cells. The effect of miR-130a-3p on tumorigenesis and VCR sensitivity was observed in vivo. Results miR-130a-3p was downregulated in VCR-resistant RB tissues and cells. Overexpression of miR-130a-3p repressed the proliferation of VCR-resistant RB cells and enhanced chemosensitivity. miR-130a-3p targeted PAX6 expression. Overexpression of PAX6 reversed the effect of miR-130a-3p on chemosensitivity of RB. Overexpression of miR-130a-3p suppressed tumor growth and reduced VCR resistance in vivo. Conclusion miR-130a-3p enhanced the chemosensitivity of RB cells to VCR by targeting PAX6 expression.

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“…1 , 2 However, there are limitations for the chemotherapy of RB, such as drug resistance and side effects. 3 Therefore, further identification of biomarkers of RB progression will be helpful for developing new molecular prognostic indicators and novel treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

LRPPRC regulates metastasis and glycolysis by modulating autophagy and the ROS/HIF1-α pathway in retinoblastoma

Song

Chen

et al. 2021

Molecular Therapy - Oncolytics

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Retinoblastoma (RB) is the most common intraocular tumor among children. Leucine-rich pentatricopeptide repeat (PPR)-motif-containing protein (LRPPRC), a suppressor gene of autophagy, has been proven to play a regulatory role in tumor progression. However, little is known about functional roles and mechanisms of LRPPRC in RB progression. First, we performed a detailed analysis for RB and normal control. The expression of LRPPRC in the RB tissues was significantly higher than that in normal tissues. Moreover, LRPPRC suppression could repress tumor cell migration, invasion, glycolysis, and reactive oxygen species (ROS)/hypoxia-inducible factor-1α (HIF1-α) pathway activation by mediating autophagy. Furthermore, overexpression of HIF1-α partially reversed the above changes induced by LRPPRC knockdown. The regulation of LRPPRC on tumor metastasis and glycolysis was also validated by a xenograft tumor assay. In summary, LRPPRC could regulate metastasis and glycolysis of RB by mediating autophagy suppression and further activating the ROS/HIF1-α pathway, and LRPPRC could be a promising prognostic biomarker for RB.

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RPL41 sensitizes retinoblastoma cells to chemotherapeutic drugs via ATF4 degradation

Cited by 9 publications

References 42 publications

Sarecycline inhibits protein translation inCutibacterium acnes70S ribosome using a two-site mechanism

Sarecycline inhibits protein translation inCutibacterium acnes70S ribosome using a two-site mechanism

Role and mechanism of miR-130a-3p in the chemosensitivity of retinoblastoma cells to vincristine

LRPPRC regulates metastasis and glycolysis by modulating autophagy and the ROS/HIF1-α pathway in retinoblastoma

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