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Page 10 of 14 Santoni et al. J Cancer Metastasis Treat 2020;6:22 I http://dx.doi.org/10.20517/2394-4722.2020.49
[38]
radiotherapy. In this regard, several miRs including miR-10b [34] and miR-92b have been suggested
as targets for the development of miRNA-based therapies. Inhibition of miR-93 enhanced the
[40]
chemosensitization of glioma cells to TMZ treatment , while miR-17-92 and its target CTGF have
[37]
been suggested for use in differentiation-promoting therapy in the treatment of GSC . Conversely, the
[40]
[33]
upregulation of miR-193b and miR-93 are associated with advanced malignancy and represent negative
prognostic factors. Ars-2, which reduces miR-6798 expression, was associated with poor overall survival in
[49]
glioma patients .
[41]
Finally, Shen et al. have suggest that the miR effect in cancer may also depend on the p53 status of
tumor cells. In glioma cell lines harboring wild-type p53, miR-149 showed pro-survival function, as it
Cip1
targeted caspase-2 via the inactivation of p53/p21 pathways, while functioning as a tumor suppressor
in proliferation and invasion of glioma cell lines with p53 mutations. miR-149 also inhibited proliferation
and migration of glioma cell lines with p53 loss, suggesting its distinct biological function within both p53
wild-type and p53 mutated glioma cells.

Cip1
LncRNAs have recently emerged as crucial players in the p21 complex signaling network as they control
glioma development and progression [71-73] , the activation of GSCs, as well as radioresistance. LncRNAs
aberrantly expressed in CSCs in different cancer types such as epatocarcinoma, are active participants
in the major signaling pathways governing DDR, DNA repair, apoptosis and epithelial-mesenchymal
transition [54,74] . It has been also reported that the deregulation of LncRNAs plays a role in cancer recurrence
[75]
and prognosis . With increasing knowledge on the expression profile of LncRNAs in cancers, their
potential roles as biomarkers in diagnosis and prognosis have been highlighted. Expression levels of
LncRNAs are closely associated with the real tumor status. Additionally, LncRNAs are more sensitive and
specific as compared to the other conventional markers. Furthermore, given that LncRNAs are released in
[75]
body fluids, this suggests their potential to be utilized in a clinical setting as non-invasive biomarkers .
In gliomas, several dysregulated LncRNAs are involved in proliferation, radioresistance, metastasis
and cancer stem cell properties. A strong correlation between high LncRNA expression and clinical
parameters has been reported for LncRNA-SNHG20 in glioma patients. High LncRNA-SNHG20 has been
associated with larger tumor size, larger extent of resection, more advanced grade (WHO classification),
poorer survival status and a higher incidence of recurrence. High SNHG20 levels are predictive of poor
[71]
prognosis and represent an independent potential prognostic biomarker for glioma patients . Similarly,
overexpression of SNHG3, SNHG6 and FAH83H-AS1, which promote the malignant phenotype, represent
a negative prognostic factors [60,61,70] .

Given the up-regulated expression of LncRNAs in glioma patients, and the role in cancer development and
progression, LncRNA inhibition (e.g., RPH, SNHG3, SNHG16, LOC441204) [57-60] would represent a novel
diagnostic and therapeutic strategy in gliomas. Moreover, as LincRNA-p21 enhances the radiosensitivity
Cip1
[69]
of hypoxic tumor cells, it represents a valuable target for radiation therapy in glioma patients .
Furthermore, in GSCs, the LncRNA-mediated effects also depend on the epigenetic regulation of genes,
particularly via recruitment of the Polycomb repressor complex and by acting as competing endogenous
RNAs for miRNAs targeting genes involved in stemness and radioresistance, mainly of the WNT/B-catenin
[76]
Cip1
and p21 pathways .
[78]
[77]
Finally, several miRs such as miR26a and LncRNAs such as Lnc-TALC have been found to promote
MGMT expression and TMZ resistance in gliomas. However, at present no miRs or LncRNAs targeting
Cip
p21 have been employed to modulate alkylating agent resistance in gliomas.
CONCLUSION
The functions of the vast majority of miRNAs, LncRNAs and LincRNAs encoded by mammalian genome
remain largely unknown. However, recent studies indicate that these transcripts play vital roles not only