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Xu et al. Radiation therapy in keloids treatment

new assumption is that primary scars are always due are not participated in protein synthesis but targeting
to congenital endothelial dysfunction, while secondary the 3’UTR of mRNA. [77] MicroRNAs were considered
scars is always caused by aging. Therefore, keloids playing roles in multiple stages of cancer development,
and hypertrophic scars tend to appear on younger including cell proliferation, apoptosis and migration.
patients, while normal scars are not. These new Reasonably, microRNA deregulation was believed to
evidence and assumptions might indicate the damage indicate clinical intervention. A number of microRNAs
towards endothelial cells or preceding blood vessels have been identified due to differentially expression
can partly explain the damage induced by radiation in keloid tissues and keloid fibroblasts. In the study
therapy. published in 2012, a total of 32 differentially expressed
in keloid tissues comparatively. [78] Among them, 23
Long non-coding RNA and microRNA miRNAs (e.g. miR-21, miR-4269, miR-382) were
Long non-coding RNA (lncRNA) and microRNA are upregulated and 9 miRNAs were downregulated (e.g.
both hot issues in the past decades, especially in miR-203, miR-205, miR-200b/c), which participated
oncology. The lncRNAs and microRNAs were both in some important signaling pathways functioning in
unearthed being involved in pathological process of wound healing process or scar formation, specifically
keloid formation, which is assumed to have potential mitogen-activated protein kinase, focal adhesion and
to partially explain the cellular response to radiation biosynthesis of collagen protein. [79] Furthermore, these
therapy. The microarray technology was first applied differential-expressed microRNAs were observed
in study of keloids in our hospital. [76] Our published as major function in keloid fibroblasts. The altered
data demonstrated that 1,731 lncRNAs constantly microRNA profiling narrowed down to 6 upregulated
upregulated and 782 downregulated, 1,079 mRNAs and 3 downregulated microRNA genes. Meanwhile,
upregulated and 3,282 downregulated in keloid microRNAs were considered playing important
respectively (fold change ≥ 2.0, P < 0.05). Some regulatory roles in various pathways, at least in cancer
selected 3 upregulated and 1 downregulated lncRNA treatment. [80] These microRNAs were functioning in
were re-confirmed by performing quantitative real time different aspects, including DNA damage response,
polymerase chain reaction (qRT-PCR). We had 55 the microenvironment and survival pathways and other
pathways highlighted in total, 11 pathways related with radioresistance-related pathways. Some microRNAs
upregulated transcripts and 44 with downregulated were reported in both the function of keloid formation
in keloid. What’s more, the CACNA1G-AS1, one of process and the response to radiation therapy
the selected lncRNA potentially functions vitally in process. For example, miR-21 is believed to promote
keloid formation. In another study working on ear-lobe phosphatidylinositol 3 kinase-AKT-pathway-mediated
keloids also by microarray, a total of 2,068 lncRNAs survivals by suppressing its direct and indirect
and 1,511 mRNAs differentially expressed between negative regulators PTEN, deemed as one of vital
earlobe keloid and normal tissues were identified. [76] survival pathways. Therefore, miR21 was regarded
Similarly, more than 1,000 lncRNAs and mRNAs as one of the most promising targets for RNA-based
were upregulated, with another several hundreds of therapy in treatment of breast cancer. Triggered by
lncRNAs and mRNAs downregulated. In this study, 35 diverse stimuli including ionizing radiation, autophagy
pathways were also highlighted. However, the lncRNAs is considered as a self-degrading process. [81] MiR-199-
regulating encoding transcripts/genes involved in Wnt 5p is also considered as an autophagy suppressor in
signaling pathway in keloids is previously reported. [35] MCF7 cells. MiR-199-5p also delivers radiosensitive
Eleven top co-expressed lncRNAs characterized potential to breast cancer cell lines. [82,83] MiR-199a-5p
with the highest co-expression coefficients to the 17 overexpression inhibits DRAM1 and Beclin1 expression
identified skin-related keloid-aberrant Wnt-genes. After in MCF7 cells and also sensitizes MDA-MB-231 cells
PCR confirmation, 4 lncRNAs including CACNA1G- to irradiation. This novel microRNA is now considered
AS1, HOXA11-AS, LINC00312 and RP11-91I11.1 with as one of the therapeutic target. [84] In another study,
their 6 paired Wnt-genes were believed to function in miR-199a-5p is believed to have an influence on the
keloid formation. These lncRNAs responded to the proliferation of keloid fibroblasts.Transfection of different
pre-designed array and qPCR test simultaneously. overly expressed miRNAs into a keloid fibroblast with
However, unluckily, no updating data generated EdU assay showed a significant downregulated cell
from post-irradiation keloid tissue or even cancer proliferation rate and altered cell cycles. [85] Moreover,
tissue supporting this assumption. But lncRNA is miR200b and miR200c, both belonging to miR200
now believed to be excellent biomarker for predicting family, were associated to aberrant proliferation
breast cancer and prostate cancer survival, which of fibroblasts and radiation-induced apoptosis,
will lead us to keep our eyes closed on this area. respectively. [86-88] MiR-200b was downregulated by
MicroRNAs are 21-23 nucleotide molecule, which more than 2-fold in hypertrophic scars, regulating the
122 Plastic and Aesthetic Research ¦ Volume 4 ¦ July 28, 2017