Page 12 - Read Online

Page 8 of 14 Santoni et al. J Cancer Metastasis Treat 2020;6:22 I http://dx.doi.org/10.20517/2394-4722.2020.49

Table 2. Long non-coding RNA and long intergenic non-coding RNA interacting with p21 Cip1 pathway in glioma
Lnc/LincRNA Mechanism/s Cell functions Ref.
SNHG3 Epigenetic p21/KLE2 repression Proliferation ↑ apoptosis ↓ [60]
RP11-732M18.3 Binding to 14.3.3 b/a Cell growth ↑ [57]
SNHG16 Caspase 3/9 reduction Proliferation and apoptosis ↑ [59]
SNHG20 p21 Cip1 silencing Proliferation ↑ [71]
PTENP1 SHG44 reduction Proliferation and metastasis ↓ [62]
FAH83H-AS1 Epigenetic p21 Cip1 silencing Poor prognosis ↑ [70]
SNH6 ND Proliferation ↓ [61]
LOC441208 Binding to b-catenin Cellgrowth ↑ [58]
p21 Cip1 Reduced HIF-1 autophagy Radiosensitivity ↑ [69]
p21 Cip1 HuR upregulation Stemness and radioresistance ↓ [51]
p21 Cip1 Binding to hnRNP-K Apoptosis ↑ [64]
ASEN Binding to UPF1 Senescence ↓ [72]
p21 Cip1 CRF/CRFR1 Proliferation and invasion ↑ [73]
↑: increase; ↓: decrease; KLE2: condensin-2 complex subunit kle-2; HIF-1: hypoxic inducible factor 1; HuR: Hu-antigen R; hnRNP-K:
heterogeneous nuclear ribonucleoprotein K; UPF1: up-frameshift suppressor 1 homolog; CFR: corticotropin-releasing factor; CRFR1: CRF
receptor 1

development and progression. Long intergenic noncoding RNAs (LincRNAs) are long RNA transcripts
which control cell differentiation and maintenance of cell identity. All of the above have recently been
found to be altered in various cancer types [Table 2] . LncRNAs have been recognized as regulators
[52]
involved in different steps of the tumorigenic process. In gliomas, the functions of most LncRNAs are not
well known, and the mechanisms controlling the proliferation, invasion, angiogenesis, radiosensitivity or
[53]
radioresistence, and GBM stemness remain poorly defined . While many LncRNAs have been identified,
only a few have been functionally described in gliomas Moreover, CSC regulation by LncRNA following
radiotherapy and the relationship between LncRNA and tumor spreading and radioresistance have been
[54]
reported .

Recent studies have evidenced that LncRNAs control the transcription of genes involved in DNA Damage
Response (DDR), the latter of which is strictly associated with radiosensitivity and repair capacity [55,56] .
The majority of LncRNAs are overexpressed in tumor cells, hence their inhibition might represent a new
therapeutic target for glioma treatment.

Among LncRNA, RP11-732M18.3 is highly overexpressed in glioma cells and functions as an oncogene by
interacting with 14-3-3β/α to promote glioma growth .
[57]
Its overexpression has been associated with the proliferation of glioma cells and tumor growth both in vitro
and in vivo. LncRNA RP11-732M18.3 stimulates the G1/S cell cycle transition and cell proliferation. It has
been found that interaction of LncRNA RP11-732M18.3 with 14-3-3β/α increases the degradation of the
Cip1
p21 protein. In fact, by promoting the recruitment of ubiquitin-conjugating enzyme E2 E1 (UBE2E1)
to 14-3-3β/α and with the binding of 14-3-3β/α with UBE2E1, LncRNA RP11-732M18.3 stimulates the
degradation of p21 Cip1[57] . Similarly, LOC441204-LncRNA, has been shown to be upregulated in glioma cell
lines. It promotes tumor cell growth by stabilizing the β-catenin pathway. LOC441204 can bind to β-catenin
Cip1
and prevent its degradation, thus resulting in downstream p21 repression and cdk4 activation that in
turn enhances glioma cell proliferation. The LOC441204 knockdown suppressed tumor cell proliferation of
[58]
glioma cell lines .

The expression of the small nucleolar RNA host gene 16, SNHG16-LncRNA was upregulated in gliomas.
Knockdown of SNHG16 is associated with high p21 Cip1 expression, poor proliferation and increased
apoptosis. Lnc-SNHG16 was shown to inhibit p21 Cip1 expression and caspase 3/9 activation, while
increasing cyclinD1/B1 expression . The SHNG3 upregulation in glioma promoted cell proliferation,
[59]