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CASC11 promotes aggressiveness of prostate cancer cells through miR-145/IGF1R axis

Prostate Cancer and Prostatic Diseases volumeĀ 24,Ā pages 891ā€“902 (2021)Cite this article

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Abstract

Background

Prostate cancer (PCa) is the most common malignancy diagnosed among men after lung cancerĀ in developed countries. Investigation of the underlying molecular mechanisms of PCa is urgently needed in order to develop better therapeutic strategies and to reveal more effective therapeutic targets. In this study, we aimed at exploring the potential functions of CASC11 in association with miR-145 and IGF1R during the malignant progression of PCa cells.

Methods

We initially investigated the oncogenic potential of noncoding members of CASC gene family and analyzed the effects of CASC11 overexpression on proliferation, migration, and colony formation ability of DU145, LNCaP, and PC3 PCa cells. We, then, exprlored the association of CASC11, miR-145, and IGF1R expression and their impacts on PI3K/AKT/mTOR signaling pathway in in vitro models.

Results

In silico analysis revealed that of the CASC family only CASC11 showed consistent results considering its differential expression as well as its association with the overall survival of patients. We demonstrated that ectopic overexpression of CASC11 significantly increased the proliferation, colony formation, and migration capacity in all three cell lines. CASC11 overexpression caused suppression of miR-145 and overexpression of IGF1R, leading to activation of PI3K/AKT/mTOR signaling pathway.

Conclusion

In summary, we found that CASC11 is upregulated in PCa cells and clinical tumor samples in comparison to corresponding controls and revealed that ectopic CASC11 overexpression promotes cellular phenotypes associated with PCa progression through CASC11/miR-145/IGF1R axis.

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Fig. 1: CASC11 servesĀ as an important candidate with oncogenic function among CASC family members.
Fig. 2: CASC11 promoted the proliferation and colony formation capacities of PCa cells.
Fig. 3: CASC11 induced the migrationĀ of PCa cells.
Fig. 4: CASC11 exertsĀ itsĀ oncogenicĀ functions through miR-145/IGF1R axis.
Fig. 5: CASC11 participates inĀ prostate carcinogenesis via dysregulation of PI3K/Akt/mTORĀ pathway.

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Authors and Affiliations

  1. Molecular Biology and Genetics Department, Erzurum Technical University, Erzurum, Turkey

    Ozel Capik,Ā Fatma SanliĀ &Ā Omer Faruk Karatas

  2. Molecular Cancer Biology Laboratory, High Technology Application and Research Center, Erzurum Technical University, Erzurum, Turkey

    Ozel Capik,Ā Fatma SanliĀ &Ā Omer Faruk Karatas

  3. Department of Pathology, Erzurum Faculty of Medicine, Health Sciences University, Erzurum, Turkey

    Ali Kurt

  4. Department of Pathology, Faculty of Medicine, Ataturk University, Erzurum, Turkey

    Onur Ceylan

  5. Department of Internal Medicine, Division of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Ilknur SuerĀ &Ā Murat Kaya

  6. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA

    Michael Ittmann

  7. Michael E. DeBakey VAMC, Houston, TX, USA

    Michael Ittmann

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Correspondence to Omer Faruk Karatas.

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OC, FS, AK, OC, IS, MK, and MI declare that they have no conflict of interests. OFK holds stocks in EcoTech Biotechnology. The terms of this arrangement have been reviewed and approved by Erzurum Technical University in accordance with its policy on objectivity in research.

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Capik, O., Sanli, F., Kurt, A. et al. CASC11 promotes aggressiveness of prostate cancer cells through miR-145/IGF1R axis. Prostate Cancer Prostatic Dis 24, 891ā€“902 (2021). https://doi.org/10.1038/s41391-021-00353-0

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