Autophagy-mediating microRNAs in cancer chemoresistance

Ye, Jing; Liang, Wenqing; Liu, Jian; Zhang, Lin; Wei, Jianguo; Yang, Jianhui; Zhang, Yu; Huang, Zhenpeng

doi:10.1007/s10565-020-09553-1

Cited by 24 publications

(14 citation statements)

References 183 publications

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“…MicroRNAs (miRNAs) are a class of short noncoding RNAs that post-transcriptionally regulate gene expression through binding to the 3 ′ -untranslated region (UTR) of target mRNAs [20][21][22]. Numerous miRNAs have been reported to be implicated in the progression of osteosarcoma and accurately predict the long-term outcome of osteosarcoma patients.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-181a-5p Promotes Osteosarcoma Progression via PTEN/AKT Pathway

Sun

Chen

et al. 2022

Analytical Cellular Pathology

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Osteosarcoma is the most common primary malignant bone tumor in children and adolescents with poor prognosis. MicroRNA-181a-5p (miR-181a-5p) is involved in the progression of various tumors; however, its role and underlying mechanism in osteosarcoma remains unclear. In this study, we found that miR-181a-5p was upregulated in human osteosarcoma cells and tissues. miR-181a-5p mimic significantly promoted, while miR-181a-5p inhibitor blocked the proliferation, colony formation, migration, invasion, and cell cycle progression of osteosarcoma cells. Mechanistically, miR-181a-5p bound to the 3 ′ -untranslational region of phosphatase and tensin homolog (PTEN) and reduced its protein expression, thereby activating protein kinase B (PKB/AKT) pathway. Either PTEN overexpression or AKT inhibition notably blocked the tumor-promoting effects of miR-181a-5p. Moreover, we observed that miR-181a-5p mimic further inhibited growth of human osteosarcoma cells in the presence of adriamycin or cisplatin. Overall, miR-181a-5p promotes osteosarcoma progression via PTEN/AKT pathway and it is a promising therapeutic target to treat osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-181a-5p Promotes Osteosarcoma Progression via PTEN/AKT Pathway

Sun

Chen

et al. 2022

Analytical Cellular Pathology

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“…In the current study, the experimental data revealed that CASK downregulation increased HCC cell apoptosis through enhancing cleaved PARP and cleaved caspase 7 activation. Although apoptosis is the most widely studied programmed cell death, recent analyses have highlighted the signi cance of additional forms of cell death, like autophagic cell death [40][41][42]. In this research, we found that CASK knockout-induced autophagy per se enhanced its cell death effect.…”

Section: Discussionmentioning

confidence: 54%

CASK Silence Enhances Chemosensitivity of Hepatocellular Carcinoma Through activating Apoptosis, Inducing JNK/c-Jun-Mediated Autophagic Cell Death and Decreasing ABCG2

Ding¹,

Bao²,

Jin³

et al. 2021

Preprint

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Background: Advanced hepatocellular carcinoma (HCC) patients usually fail to be treated because of drug resistance, including sorafenib. Methods: The expression and prognostic role of calcium/calmodulin-dependent serine protein kinase (CASK) in HCC were assessed by combination of bioinformatic analysis and experimental validation. The effects of CASK in regulating proliferation, apoptosis and drug resistance of HCC cells in vitro and in vivo were investigated using gain- or loss-of-function strategies by performing lots of specific methods including Cell Counting kit-8 (CCK8), colony formation assay, flow cytometry, transmission electron microscopy, immunofluorescent confocal laser microscopy and tumor xenograft experiments, immunohistochemistry staining. Moreover, the underlying molecular mechanisms responsible for CASK’s functions in HCC were also explored. Results: Currently, we discovered that CASK was positively associated with sorafenib resistance of HCC in vitro and in vivo, and was significantly related with poor prognosis in HCC. Moreover, inhibition of CASK can increase the effect of sorafenib partially by promoting apoptosis and autophagy, while CASK overexpression presented the opposite results. Besides, all the pan-caspase inhibitor Z-VAD-FMK, autophagy inhibitor 3-Methyladenine (3-MA) and small interfering RNA (siRNA) of LC3B reversed CASK knockout-induced effects with sorafenib treatment, suggesting that both apoptosis and autophagy were involved in CASK-mediated above functions and autophagy played a pro-death role in this research. Intriguingly, similar results were observed in vivo. In molecular level, CASK knockout activated the c-Jun N-terminal kinase (JNK) pathway, and treatment with JNK inhibitor SP600125 or transiently transfected with si-JNK significantly attenuated CASK knockout-mediated autophagic cell death. Besides, knockout of CASK dramatically inhibited the expression of ATP binding cassette subfamily G member 2 (ABCG2) and reversed of multidrug-resistance (MDR) of HCC. Conclusions: Collectively, all these results together indicated that CASK might be a promising biomarker for HCC patients and a potential therapeutic target for relieving drug resistance of HCC.

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“…In the current study, the experimental data revealed that CASK downregulation increased HCC cell apoptosis through enhancing cleaved caspase 7 activation. Although apoptosis is the most widely studied programmed cell death, recent analyses have highlighted the significance of additional forms of cell death, like autophagic cell death ( 36 – 38 ). In this research, we found that CASK knockout-induced autophagy per se enhanced its cell death effect.…”

Section: Discussionmentioning

confidence: 99%

CASK Silence Overcomes Sorafenib Resistance of Hepatocellular Carcinoma Through Activating Apoptosis and Autophagic Cell Death

et al. 2021

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Hepatocellular carcinoma (HCC) patients usually fail to be treated because of drug resistance, including sorafenib. In this study, the effects of CASK in HCC were investigated using gain- or loss-of-function strategies by performing cell counting kit-8 assay, colony formation assay, flow cytometry, transmission electron microscopy, immunofluorescent confocal laser microscopy, tumor xenograft experiment and immunohistochemistry staining. The current results suggested that CASK expression was positively associated with sorafenib resistance and poor prognosis of HCC. Moreover, inhibition of CASK increased the role of sorafenib partially by promoting apoptosis and autophagy, while CASK overexpression presented the opposite effects. Besides, when treatment with sorafenib, inhibition of apoptosis using the pan-caspase inhibitor Z-VAD-FMK and inhibition of autophagy using autophagy inhibitor 3-Methyladenine (3-MA) or small interfering RNA (siRNA) of LC3B all significantly reversed CASK knockout-induced effects, suggesting that both apoptosis and autophagy were involved in CASK-mediated above functions and autophagy played a pro-death role in this research. Intriguingly, similar results were observed in vivo. In molecular level, CASK knockout activated the c-Jun N-terminal kinase (JNK) pathway, and treatment with JNK inhibitor SP600125 or transiently transfected with siRNA targeting JNK significantly attenuated CASK knockout-mediated autophagic cell death. Collectively, all these results together indicated that CASK might be a promising biomarker and a potential therapeutic target for HCC patients.

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Autophagy-mediating microRNAs in cancer chemoresistance

Cited by 24 publications

References 183 publications

MicroRNA-181a-5p Promotes Osteosarcoma Progression via PTEN/AKT Pathway

MicroRNA-181a-5p Promotes Osteosarcoma Progression via PTEN/AKT Pathway

CASK Silence Enhances Chemosensitivity of Hepatocellular Carcinoma Through activating Apoptosis, Inducing JNK/c-Jun-Mediated Autophagic Cell Death and Decreasing ABCG2

CASK Silence Overcomes Sorafenib Resistance of Hepatocellular Carcinoma Through Activating Apoptosis and Autophagic Cell Death

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