Page 15 - Read Online

Santoni et al. J Cancer Metastasis Treat 2020;6:22 I http://dx.doi.org/10.20517/2394-4722.2020.49 Page 11 of 14

in cellular physiology, but also in cancer pathology. In this regard, alternations in their regulation have
been found to be implicated in the development and progression of glioma [53,79,80] . Complex cross-talk and
Cip1
interplay between miRNAs, Lnc/LincRNAs and p21 orchestrate the regulation of protein expression and
functions in cancer cells. Our understanding of the functional roles and molecular mechanisms of miR
Cip1
and LncRNAs in glioma and GSC is still nascent. Several findings indicate that miRs targeting p21 and
more recently LncRNAs signatures correlate with glioma malignancy grade, histological differentiation
and prognosis [47,51,70] . Further in-depth investigation into miRs, LncRNAs and LincRNAs, their complex
mechanisms of regulation, as well as their involvement in glioma genesis, metastatic spread and therapeutic
resistance will be necessary in order to develop novel and effective diagnostic and therapeutic strategies
against primary and secondary GBM tumors.

DECLARATIONS
Authors’ contributions
Supervised the work and wrote the manuscript: Santoni G
Contributed to the preparation of the subchapters: Morelli MB, Amantini C
Contributed to the preparation of figures and tables: Maggi F, Marinelli O
Provided critical revision of the manuscript: Nabissi M
Collaborated in the Drafting of the introduction and conclusion: Santoni M

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by PRIN 2017 and Fondazione Umberto Veronesi (Post-doctoral Fellowship 2019
to Morelli MB).

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

REFERENCES
1. Ostrom QT, Gittleman H, Stetson L, Virk SM, Barnholtz-Sloan JS. Epidemiology of gliomas. Cancer Treat Res 2015;163:1-14.
2. Reni M, Mazza E, Zanon S, Gatta G, Vecht CJ. Central nervous system gliomas. Crit Rev OncolHematol 2017;113:213-34.
3. Scherer HJ. A critical review: the pathology of cerebral gliomas. J Neurol Neurosurg Psychiatry 1940;3:147-77.
4. Morrison SJ, Kimble J. Asymmetric and symmetric stem-cell divisions in development and cancer. Nature 2006;441:1068-74.
5. Qian X, Hulit J, Suyama K, Eugenin EA, Belbin TJ, et al. P21/CIP1 mediates reciprocal switching between proliferation and invasion
during metastasis. Oncogene 2013;32:2292-303.
6. Pei XH, Xiong Y. Biochemical and cellular mechanisms of mammalian CDK inhibitors: a few unresolved issues. Oncogene
2005;24:2787-95.
7. Romanov VS, Pospelov VA, Pospelova TV. Cyclin dependent kinase inhibitors (CKIs) play a crucial role in the regulation of the cell
cycle in non transformed cells and are implicated in suppression of cell proliferation under stress conditions caused by growth factor
deficiency. Biochemistry (Mosc) 2012;77:575-84.
8. Abbas T, Dutta A. p21 in cancer: Intricate networks and multiple activities. Nat Rev Cancer 2009;6:400-14.