ArticleOncotarget2015
Computational prediction and experimental validation of a novel synthesized pan-PIM inhibitor PI003 and its apoptosis-inducing mechanisms in cervical cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- PIM Kinase Inhibitors as Novel Promising Therapeutic Scaffolds in Cancer Therapy.Current topics in medicinal chemistry · 2024Review
- Identification of Circulating Exosomal microRNAs Associated with Radioiodine Refractory in Papillary Thyroid Carcinoma.Journal of personalized medicine · 2022Article
- Network pharmacology of triptolide in cancer cells: implications for transcription factor binding.Investigational new drugs · 2021Article
- Hsa_circ_0000520 overexpression increases CDK2 expression via miR-1296 to facilitate cervical cancer cell proliferation.Journal of translational medicine · 2021Article
- The role and underlying mechanism of miR-1299 in cancer.Future science OA · 2021Review
- CUL4A regulates endometrial cancer cell proliferation, invasion and migration by interacting with CSN6.Molecular medicine reports · 2021Article
- 6 Circulating miRNAs can be used as Non-invasive Biomarkers for the Detection of Cervical Lesions.Journal of Cancer · 2021Article
- Long non-coding RNA NPBWR1-2 affects the development of ovarian cancer via multiple microRNAs.Oncology letters · 2020Article
- The tumor-suppressive function of miR-1296-5p by targeting EGFR and CDK6 in gastric cancer.Bioscience reports · 2019Article
- MicroRNA-1296 Facilitates Proliferation, Migration And Invasion Of Colorectal Cancer Cells By Targeting SFPQ.Journal of Cancer · 2018Article
- MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway.Molecular cancer · 2017Article
- Epigenetic sampling effects: nephrectomy modifies the clear cell renal cell cancer methylome.Cellular oncology (Dordrecht, Netherlands) · 2017Article
- MicroRNA-1299 is a negative regulator of STAT3 in colon cancer.Oncology reports · 2017Article
- miR-1296-5p decreases ERBB2 expression to inhibit the cell proliferation in ERBB2-positive breast cancer.Cancer cell international · 2017Article
- miR 1296-5p Inhibits the Migration and Invasion of Gastric Cancer Cells by Repressing ERBB2 Expression.PloS one · 2017Article
- Characterization of HJ-PI01 as a novel Pim-2 inhibitor that induces apoptosis and autophagic cell death in triple-negative human breast cancer.Acta pharmacologica Sinica · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PIM protein family, short-lived serine/threonine kinases (PIM1, PIM2 and PIM3), are weak oncogenes but contribute to tumorigenesis as cancer targets. Thus, design of a novel pan-PIM inhibitor is still a challenge for current cancer drug discovery. Herein, we used a Naïve Bayesian model to construct the PIM network and identified Bad and Hsp90 to interact with PIMs. Then, we screened a series of candidate small-molecule compounds targeting PIMs, and subsequently synthesized a novel small-molecule compound PI003 with remarkable anti-proliferative activities in cervical cancer cells. Moreover, we found that PI003 induced apoptosis via the death-receptor and mitochondrial pathways by targeting PIMs and affecting Bad and Hsp90. Combined with microRNA microarray analyses, we demonstrated that some microRNAs such as miR-1296 and miR-1299 could affect PIM1-STAT3 pathway in PI003-induced apoptosis. Finally, we reported that PI003 had remarkable anti-tumor activity and apoptosis-inducing effect in in vivo mouse model. In conclusion, these results demonstrate that PI003, as a novel synthesized pan-PIM inhibitor, induces the death-receptor and mitochondrial apoptosis involved in microRNA regulation, and also possessed remarkable anti-tumor activity and apoptosis-inducing effect in vivo. Thus, these findings would shed light on discovering more potential new small-molecule pan-PIM inhibitors in future cervical cancer therapy.
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