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Cited by 19Cancer-related Molecular PathwaysCancer Mechanisms and TherapyPI3K/AKT/mTOR signaling in cancer

Downregulation of Pim-2 induces cell cycle arrest in the G0/G1 phase via the p53-non-dependent p21 signaling pathway

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Liu, Zhaoyun, Liu, Hui, Yuan, Xin, Wang, Yihao, Li, Lijuan, Wang, Guojin, Song, Jia, Shao, Zonghong +1 more·2018·Oncology Letters
DOI 10.3892/ol.2018.7865PMC PMC5835926
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Abstract

Pim-2 is a serine/threonine protein kinase that is highly expressed in various types of cancer, with essential roles in the regulation of signal transduction cascades, which promote cell survival and proliferation. The present study demonstrated that Pim‑2 was expressed in cells lines derived from hematopoietic tumors and lung cancer. In vitro, downregulation of Pim‑2 by short interfering RNA inhibited proliferation and delayed G0/G1 cell cycle progression in K562 leukemia, RPMI‑8226 multiple myeloma, and H1299 and A549 non‑small cell lung carcinoma cell lines. Furthermore, downregulation of Pim‑2 resulted in upregulation of cyclin‑dependent kinase (CDK) inhibitor p21, irrespective of the p53 status. In addition, the present study revealed that CDK2 and phosphorylated retinoblastoma (pRb) were significantly downregulated. This finding suggested that inhibition of CDK2 and pRb expression via upregulated p21 was involved in the downregulation of Pim‑2‑induced G0/G1 cell cycle arrest in lung cancer and hematopoietic malignancy cells. These results suggested that Pim‑2 may serve a role in hematopoietic tumors, lung cancer proliferation and cell cycle progression by regulating the p21 signaling pathway. Downregulation of Pim‑2 decreased cancer cell proliferation. Therefore, Pim‑2 may be a potential therapy target in clinical cancer therapy.

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  • p21 also causes cell-cycle arrest in G0 in different settings.

    “p21 also causes cell-cycle arrest in G 0 in different settings (43,44)”

    From <i>Txnip</i> Enhances Fitness of <i>Dnmt3a</i> -Mutant Hematopoietic Stem Cells via <i>p21</i> (2022) · cites this paper as [43]

    The Introduction attributes G0/G1 cell-cycle arrest after Pim-2 downregulation to the p21 signaling pathway, and the Results report increased G0/G1 populations in all four cell lines tested. The paper does not distinguish arrest in G0 specifically from arrest in G1, so it does not establish the claim as phrased. (LLM, conf=0.86)

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References 35 · Cited by 19

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Authors
Liu, Z., Liu, H., Yuan, X., Wang, Y., Li, L., Wang, G., Song, J., Shao, Z., & Fu, R.
Affiliations
Tianjin Medical University General Hospital (CN)
Corresponding author
Fu, Rong
ORCID
Venue
Oncology Letters
Publisher
Spandidos Publications
Published
2018-01-26
Volume
15
Issue
4
Pages
4079-4086
ISSN
  • 1792-1074 (ISSN-L)
  • 1792-1082
DOI
10.3892/ol.2018.7865
PMC
PMC5835926
OpenAlex
W2786188568
Cited by
19
References
35
Citations by year
2024: 1 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 1
FWCI
1.13
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Oncology Letters (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (14JCYBJC25400, 15JCYBJC24300, 12ZCDZSY18000, 81400085, 81400088, 81570106)
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
PIM2, p21, G0/G1 cell cycle arrest, CDK2, retinoblastoma protein phosphorylation, p53-independent signaling, hematopoietic tumors, multiple myeloma, leukemia, non-small cell lung cancer, cell proliferation, kinase inhibitors, cancer therapy targets

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