Knockdown of PYCR1 suppressed the malignant phenotype of human hepatocellular carcinoma cells via inhibiting the AKT pathway activation

Guo, Jiang; Cheng, Xiaoyan; Tian, Yanjie; Li, Baoming; Zhang, Xiaoli; Gao, Xuesong; An, Yunhe

doi:10.1016/j.repbio.2021.100534

Cited by 6 publications

(6 citation statements)

References 8 publications

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“…Specific molecular pathways by which PYCR1 promotes the malignant phenotype of tumor cells have been documented earlier; for instance, in liver cancer, PYCR1 activates the AKT pathway 36 and the c‐Jun N‐terminal kinase/insulin receptor substrate 1 (JNK/IRS1) pathway 22 ; in colon cancer, PYCR1 increases cancer cell proliferation, drug resistance, and epithelial mesenchymal transition by activating the STAT3‐mdiated p38 MAPK and NF‐κB signaling pathway 37 . PYCR1 mediates Mitochondrial Lon‐induced production and release of reactive oxygen‐dependent inflammatory factors (transforming growth factor, IL‐6, IL‐13, and VEGF‐A), which further increase M2 macrophage polarization and generate an immunosuppressive milieu, hence increasing tumor angiogenesis, metastasis, and immunosuppression 23 .…”

Section: Discussionmentioning

confidence: 77%

“…Therefore, we chose the RP11-498C9.17 plasmid that does not overlap with PYCR1 as a control group. Specific molecular pathways by which PYCR1 promotes the malignant phenotype of tumor cells have been documented earlier; for instance, in liver cancer, PYCR1 activates the AKT pathway 36 and the c-Jun N-terminal kinase/insulin receptor substrate 1 (JNK/IRS1) pathway 22 ; in colon cancer, PYCR1 increases cancer cell proliferation, In human normal fibroblasts, where PYCR1 and PYCR2 bind to create ribonucleotide reductase small subunit B to protect cells from oxidative stress-induced damage, adequate expression of PYCR1 is advantageous for the maintenance of antioxidant capacity. In addition, by oxidizing NADH and generating proline, PYCR1 supports mitochondrial oxidative respiration to supply energy under hypoxia.…”

Section: Discussionmentioning

confidence: 78%

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Antisense lncRNA‐RP11‐498C9.13 promotes bladder cancer progression by enhancing reactive oxygen species‐induced mitophagy

Song

Yang

et al. 2023

The Journal of Gene Medicine

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BackgroundUrinary system's most prevalent malignant tumor is bladder cancer. The enzyme pyrroline‐5‐carboxylate reductase 1 (PYCR1) has pro‐tumorigenic characteristics. In the present study, the upstream and downstream regulatory mechanisms of PYCR1 in bladder cancer were investigated.MethodsThe relationship between the expression of PYCR1 in bladder cancer and its prognosis was analyzed using a bioinformatics technique. Plasmid transfection and small interfering RNA were utilized to overexpress and silence genes, respectively. Utilizing MTT, colony formation, EdU, and transwell assays, the proliferation and invasiveness of bladder cancer cells were evaluated. Employing an RNA pull‐down experiment and RNA immunoprecipitation, the relationship between RNAs was analyzed. Fluorescence in situ hybridization, immunohistochemistry, and western blotting were used to detect protein expression and localization. Flow cytometry was used to identify reactive species (ROS) expression in cells. Mitophagy was detected using immunofluorescence.ResultsPYCR1 was highly expressed in bladder cancer tissue and was related with a poor prognosis for the patient. By binding to PYCR1, the antisense RNA lncRNA‐RP11‐498C9.13 prevented the degradation of PYCR1 and promoted its production. Down‐regulation of lncRNA‐RP11‐498C9.13 and PYCR1 inhibited the proliferation and invasiveness of bladder cancer cells and decreased tumorigenesis. In addition, it was found that the lncRNA‐RP11‐498C9.13/PYCR1 axis promoted ROS generation and induced mitophagy in bladder cancer cells.ConclusionsWe demonstrated that lncRNA‐RP11‐498C9.13 promoted bladder cancer tumorigenesis by stabilizing the mRNA of PYCR1 and promoted ROS‐induced mitophagy. The lncRNA‐RP11‐498C9.13/PYCR1/mitophagy axis was anticipated to be a significant therapeutic target for bladder cancer.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 78%

Antisense lncRNA‐RP11‐498C9.13 promotes bladder cancer progression by enhancing reactive oxygen species‐induced mitophagy

Song

Yang

et al. 2023

The Journal of Gene Medicine

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“…Increasing evidence suggested that PYCR1 was highly expressed in various cancers, such as prostate cancer (Zeng et al 2017), non-smallcell lung cancer (NSCLC) (Cai et al 2018) and hepatocellular cancer (Zhuang et al 2019). For example, previous research demonstrated that silencing of PYCR1 inhibited the proliferation, invasive migration capability, epithelial-mesenchymal transition, and metastatic abilities in hepatocellular carcinoma (HCC) (Guo et al 2021). Besides, PYCR1 was also reported to be over-expressed in NSCLC, and promoted the development of NSCLC by activating p38 pathway (Wang et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of the Roles of Oxidative stress related genes and Prognostic Value in Clear Cell Renal Cell Carcinoma

Wang

Deng

Lü

et al. 2023

Preprint

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Background：As the most common diagnosed subtype in renal cell carcinoma, clear cell renal cell carcinoma (ccRCC) patients suffer from the threat of tumor metastasis and recrudesce. Previous research has established that oxidative stress could induce tumorigenesis in many cancers and can be a cancer therapeutic target. Despite these, little progress has been made in the association of oxidative stress related genes (OSRGs) with ccRCC. Methods：MTT survival assay, qRT-PCR, apoptosis assay, cell cycle assay, ROS assay, IHC staining, were used in vitro experiments. Results：In our study, 12 differentially expressed oxidative stress-related genes (DEOSGs) and related transcription factors (TFs) relevant to overall survival (OS) were screened, as well as their mutual regulatory networks were structured by data from the TCGA database. Moreover, we constructed the risk model of the OSRGs, and performed clinical prognostic analysis and validation. Next, we correlated MELK, PYCR1, and PML with immune infiltration in ccRCC. Tissue microarray also verified the high expression of MELK and PYCR1 in ccRCC. Finally, cellular experiment in vitro demonstrated that knockdown of MELK or PYCR1 significantly inhibited ccRCC cell proliferation by causing cell apoptosis and inducing G1 phase cycle arrest. The intracellular ROS levels were elevated after knockdown of the two genes. Consulsion: Our results presented a potential application of DEORGs in prognostic prediction for ccRCC and identified two biomarkers named PYCR1 and MELK, which could regulate the proliferation of ccRCC by affecting the ROS levels. Further, PYCR1 and MELK could be promising to predict the progression and prognosis of ccRCC, thereby serving as new targets for medical treatments.

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“…Another group observed that PYCR1 gene silencing could inhibit the proliferation of hepatoma cells, promote apoptosis, and significantly inhibit the volume and size of transplanted tumors in nude mice by regulating the JNK/IRS1 pathway [ 10 ]. At the same time, the PYCR1 gene silence also can constrain the invasion and migration of HCC cells, promote apoptosis and G1 arrest [ 14 ]. Because PYCR1 plays a cancer-promoting role in HCC, PYCR1 inactivation may become a molecular target for liver cancer therapeutic.…”

Section: Discussionmentioning

confidence: 99%

“…For example, PYCR1 was downregulated by miR-488, which promoted cell proliferation and inhibited cell apoptosis, and activated the p38/MAPK pathway in non-small-cell lung cancer (NSCLC) [ 13 ]. In HCC, PYCR1 gene interference can restrain the malignant phenotype of HCC cells by inhibiting activation of the Akt pathway [ 14 ]. Another study discovered that the PYCR1 gene deletion suppresses cell proliferation and encourages cell apoptosis of HCC cells by the c-Jun N-terminal kinase/insulin receptor substrate1 (JNK/IRS1) pathway [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Shikonin induces apoptosis and autophagy via downregulation of pyrroline-5-carboxylate reductase1 in hepatocellular carcinoma cells

et al. 2022

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Shikonin(SK) is a natural small molecule naphthoquinone compound, which has anti-cancer activity in various human malignant tumors. Pyrroline-5-carboxylate reductase 1(PYCR1) is involved in tumorigenesis and regulates various cellular processes, including growth, invasion, migration, and apoptosis. However, the effect of SK and PYCR1 on apoptosis and autophagy in hepatocellular carcinoma are unclear. Our goal is to determine the internal molecular mechanism of the interaction between SK and PYCR1 and its role in the occurrence and development of liver cancer. The CCK8 assay, wound healing assay, and transwell assays show that SK and siPYCR1(gene silence PYCR1) inhibited the malignant phenotype of HCC cells, including cell viability, colony formation, migration, and invasion, respectively. The flow cytometry assays and immunofluorescence show that SK and siPYCR1 activated apoptosis and autophagy, respectively. SK induces apoptosis and autophagy in a dose-dependent manner. In addition, HCC cells were transfected with small interference fragment PYCR1 siRNA to construct siPYCR1 and SK single treatment group and co-treatment group to verify the interaction between SK and PYCR1. The Western blot identified that PI3K/Akt/mTOR signal pathway protein expression was significantly downregulated in HCC cells treated with SK and siPYCR1 together. Collectively, SK may induce apoptosis and autophagy by reducing the expression of PYCR1 and suppressing PI3K/Akt/mTOR. Thus, SK may be a promising antineoplastic drug in Hepatocellular carcinoma (HCC). SK downregulating PYCR1 might supply a theoretical foundation for the potential therapeutic application in hepatocellular carcinoma.

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Knockdown of PYCR1 suppressed the malignant phenotype of human hepatocellular carcinoma cells via inhibiting the AKT pathway activation

Cited by 6 publications

References 8 publications

Antisense lncRNA‐RP11‐498C9.13 promotes bladder cancer progression by enhancing reactive oxygen species‐induced mitophagy

Antisense lncRNA‐RP11‐498C9.13 promotes bladder cancer progression by enhancing reactive oxygen species‐induced mitophagy

Integrated Analysis of the Roles of Oxidative stress related genes and Prognostic Value in Clear Cell Renal Cell Carcinoma

Shikonin induces apoptosis and autophagy via downregulation of pyrroline-5-carboxylate reductase1 in hepatocellular carcinoma cells

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