Cathepsin L-mediated resistance of paclitaxel and cisplatin is mediated by distinct regulatory mechanisms

Zhao, Yifan; Zhu, Ying; Wang, Anqi; Xiong, Yajie; Wang, Long; Yao, Fei; Wang, Yan; Wang, Wenjuan; Lin, Fang; Liang, Zhong‐Qin

doi:10.1186/s13046-019-1299-4

Cited by 16 publications

(8 citation statements)

References 40 publications

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“…Moreover, previous research demonstrated that miR-149-5p increased the chemosensitivity of cisplatin on oral squamous cell carcinoma via inhibiting TGF-b2, p-Smad2, and p-Smad3 (Luo et al, 2019). Silencing TGF-b or smad3 in A549/TAX (paclitaxel resistant) cells decreased the expression of cathepsin L and enhanced their sensitivity to paclitaxel (Zhao et al, 2019). In addition, an expression vector carrying mutated or wild-type Smad3 was constructed and transfected into osteosarcoma cells.…”

Section: Discussionmentioning

confidence: 99%

miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3

et al. 2020

Front. Pharmacol.

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Background: MicroRNAs are known to regulate carcinogenesis of osteosarcoma. Although, miR-16-5p is known to exert inhibitory effects on several forms of cancers, its effects on the growth and invasion of osteosarcoma have not been studied. Methods: We collected human osteosarcoma specimens and adjacent tissues to detect the expression of miR-16-5p by real-time polymerase chain reaction, immunoblotting, and immunohistochemistry. The proliferation, migration, and invasion of MG63 and HOS cells following miR-16-5p overexpression and inhibition were detected with cell counting kit-8, wound healing assay, and Transwell assay, respectively. An expression vector carrying a mutated 3′-untranslated region of mothers against decapentaplegic homolog 3 (Smad3) was constructed. Results: The results showed that miR-16-5p expression was downregulated in osteosarcoma tissues and cells as compared with adjacent counterparts, while Smad3 was overexpressed in osteosarcoma cells. The overexpression of miR-16-5p resulted in the inhibition of the proliferation, migration, and invasion of osteosarcoma cells and enhanced the therapeutic effect of cisplatin. These effects were attenuated with miR-16-5p expression inhibition. In cells transfected with miR-16-5p mimic, Smad3 expression decreased, while this effect was absent in the cells carrying mutated Smad3. Conclusions: Therefore, miR-16-5p inhibits the growth and invasion of osteosarcoma by targeting Smad3.

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Section: Discussionmentioning

confidence: 99%

miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3

et al. 2020

Front. Pharmacol.

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“…Interestingly, BbCI, which is also present in the seeds of B. bauhinioides and exhibits 84% primary structure similarity with BbKI [36], demonstrates a distinguished inhibitory specificity by inhibiting cysteine protease cathepsin L and serine proteases elastase and cathepsin G [17]. Although increasing cathepsin L-like activity may be correlated with malignant tumors [37,38] and elastase [28], rBbKl did not affect L929 cell viability, proliferation, or cell adhesion. Thus, the inhibitory specificity of rBbKI may have impacted its toxicity towards fibrosarcoma cells.…”

Section: Discussionmentioning

confidence: 96%

Differences in the Inhibitory Specificity Distinguish the Efficacy of Plant Protease Inhibitors on Mouse Fibrosarcoma

Bonturi

Nakahata

et al. 2021

Plants

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Metastasis, the primary cause of death from malignant tumors, is facilitated by multiple protease-mediated processes. Thus, effort has been invested in the development of protease inhibitors to prevent metastasis. Here, we investigated the effects of protease inhibitors including the recombinant inhibitors rBbKI (serine protease inhibitor) and rBbCI (serine and cysteine inhibitor) derived from native inhibitors identified in Bauhinia bauhinioides seeds, and EcTI (serine and metalloprotease inhibitor) isolated from the seeds of Enterolobium contortisiliquum on the mouse fibrosarcoma model (lineage L929). rBbKI inhibited 80% of cell viability of L929 cells after 48 h, while EcTI showed similar efficacy after 72 h. Both inhibitors acted in a dose and time-dependent manner. Conversely, rBbCI did not significantly affect the viability of L929 cells. Confocal microscopy revealed the binding of rBbKI and EcTI to the L929 cell surface. rBbKI inhibited approximately 63% of L929 adhesion to fibronectin, in contrast with EcTI and rBbCI, which did not significantly interfere with adhesion. None of the inhibitors interfered with the L929 cell cycle phases. The synthetic peptide RPGLPVRFESPL-NH2, based on the BbKI reactive site, inhibited 45% of the cellular viability of L929, becoming a promising protease inhibitor due to its ease of synthesis.

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“…However, the function of CTSL in the complex process of tumorigenesis is not yet fully understood ( 23 ). It has been recently observed that CTSL is closely correlated with drug resistance in NSCLC ( 24 ). Our analyses showed that the upregulation of CTSL mRNA levels in LADC patients was associated with a higher risk of relapse and worse OS.…”

Section: Discussionmentioning

confidence: 99%

Establishing a Macrophage Phenotypic Switch-Associated Signature-Based Risk Model for Predicting the Prognoses of Lung Adenocarcinoma

Zhou

Liu

2022

Front. Oncol.

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BackgroundTumor-associated macrophages are important components of the tumor microenvironment, and the macrophage phenotypic switch has been shown to correlate with tumor development. However, the use of a macrophage phenotypic switch-related gene (MRG)-based prognosis signature for lung adenocarcinoma (LADC) has not yet been investigated.MethodsIn total, 1,114 LADC cases from two different databases were collected. The samples from TCGA were used as the training set (N = 490), whereas two independent datasets (GSE31210 and GSE72094) from the GEO database were used as the validation sets (N = 624). A robust MRG signature that predicted clinical outcomes of LADC patients was identified through multivariate COX and Lasso regression analysis. Gene set enrichment analysis was applied to analyze molecular pathways associated with the MRG signature. Moreover, the fractions of 22 immune cells were estimated using CIBERSORT algorithm.ResultsAn eight MRG-based signature comprising CTSL, ECT2, HCFC2, HNRNPK, LRIG1, OSBPL5, P4HA1, and TUBA4A was used to estimate the LADC patients’ overall survival. The MRG model was capable of distinguishing high-risk patients from low-risk patients and accurately predict survival in both the training and validation cohorts. Subsequently, the eight MRG-based signature and other features were used to construct a nomogram to better predict the survival of LADC patients. Calibration plots and decision curve analysis exhibited good consistency between the nomogram predictions and actual observation. ROC curves displayed that the signature had good robustness to predict LADC patients’ prognostic outcome.ConclusionsWe identified a phenotypic switch-related signature for predicting the survival of patients with LADC.

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Cathepsin L-mediated resistance of paclitaxel and cisplatin is mediated by distinct regulatory mechanisms

Cited by 16 publications

References 40 publications

miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3

miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3

Differences in the Inhibitory Specificity Distinguish the Efficacy of Plant Protease Inhibitors on Mouse Fibrosarcoma

Establishing a Macrophage Phenotypic Switch-Associated Signature-Based Risk Model for Predicting the Prognoses of Lung Adenocarcinoma

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