Role of lncRNAs in Thyroid Cancer
Military Hospital, Palampur, Himachal Pradesh, India
- *Corresponding Author:
- Murali Krishna
Surgical Specialist, Military Hospital, Palampur, Himachal Pradesh, India.
E-mail: [email protected]
Received date: March 14, 2016; Accepted date: April 19, 2016; Published date: April 22, 2016
Citation: Krishna M (2018) Role of lncRNAs in Thyroid Cancer. J Clin Epigenet 4:6. doi: 10.21767/2472-1158.100091
Thyroid cancer is the most common endocrine cancer in the word and its incidence is on the rise. Though generally associated with a very good prognosis, few cases may demonstrate resistance to treatment such as radio-iodine therapy. lncRNAs have shown to be involved in several steps of thyroid carcinogenesis. It can act as a prognostic and diagnostic marker. Altered levels of specific lncRNAs have also shown to be associated with resistance to radioiodine treatment. Therapy with lncRNA has also shown to return radio-sensitivity in thyroid cancer cell lines.
Thyroid; Papillary; lncRNA; I-131; Metast
Role of lncRNAs in Thyroid Cancer
Thyroid cancer is the most common endocrine cancer in the
world . In United States, the incidence of thyroid cancer is on
the rise due to several factors ranging from increased diagnosis to environmental exposure . Broadly, thyroid cancer has been
divided into well differentiated cancers and poorly differentiated
cancers. Among the well differentiated cancers, papillary thyroid
carcinoma (PTC) is the most common amounting to 80% of all
thyroid cancers followed by follicular carcinoma. While PTC has
more of localised metastasis, follicular carcinoma is known to
have widespread systemic metastasis. Well differentiated thyroid
carcinoma has a relatively good prognosis following surgery and
radioiodine therapy with a 10 year survival rate of more than
90% . Among the more aggressive tumours comes anaplastic
thyroid carcinoma. These tumours are refractory to radioiodine
therapy and usually have a poor prognosis. Other rare tumors
of thyroid include lymphoma, squamous cell carcinoma and
As in all malignancies genetic alterations are an integral part of
thyroid cancer also. The specific pathways involved in thyroid
carcinogenesis include genetic rearrangements in RET/PTC and
PAX8/PPARδ pathways, aberrant signalling in PI3K/Akt and
MAPK/ERK pathways . lncRNAs have also shown to play an
important part thyroid carcinogenesis. lncRNAs are non coding
RNAs with a nucleotide length more than 200 base pairs. What
was earlier thought to be ‘junk DNA’, has shown to be involved
in almost all facets of human physiology and pathology. lncRNAs
have been seen as a key in understanding the exact pathogenesis
of tumours. They also serve as a biomarker for tumours and could
in the near future be used a therapeutical tool.
Studies have shown that almost 240 lncRNAs have an altered expression in PTC. Few of the lncRNAs shown to be involved in thyroid tumour are given in table below (Table 1).
Table 1: List of lncRNAs upregulated and downregulated in thyroid cancer.
Specific genetic mutations have known to predispose patients to
PTC. One such mutation is the single nucleotide polymorphism
(SNP) rs965513 in 9q22 (28–30). This is associated with
nearby FOXE1 gene. FOXE1 gene plays an essential part during
embryonic development of thyroid and regulates several thyroid
specific genes [7-32]. Further studies on the exact mechanism
revealed the locus 9q22 to code for lncRNA PTCSC2 . The role
of this lncRNA is akin to a tumour suppressor and it was found
to be absent or decreased in thyroid cancer cell lines. lncRNA
PTCSC2 may be another missing link in understanding the exact
pathogenesis of thyroid cancer.
Kim et al. conducted a study looking into the differential
expression of lncRNAs . It showed that LOC100507661 was
over expressed in papillary and anaplastic thyroid cancers. Also
patients with this specific over expression had increased lymph node metastasis and BRAF V600E mutation. They concluded
that LOC100507661 played an important part in carcinogenesis
of thyroid cancers and can act as a prognostic marker. Another
similar study by Du et al.  used the RNA sequencing profile
of PTC patients and compared it to a healthy cohort. It showed
an altered expression of almost 240 lncRNAs. Further gene
ontology analysis was used to investigate the related genes and
a functional lncRNA-mRNA co expression network was used to
investigate clinical relevance. The study validated differential
expression of five lncRNAs namely CTD-3193O13.11, RP5-
1024C24.1, AC007255.8, HOXD-AS1 and RP11-402L6.1. Also the
varied expression of these lncRNAs were related to clinical stage,
lymph node metastasis and tumour size .
Lungs are the most common site of distant metastasis in a case of
Differentiated thyroid cancer (DTC) . Radioiodine therapy with
I-131 is the main treatment in these cases. However around onethird
of such metastatic cases do not respond to I-131. At present
to identify these non responders require a radioiodine scan. A
study by Qiu et al.  has shown a differential expression of four
lncRNAs in patients with non I-131 avid lung metastasis namely
ENST00000462717, ENST00000415582, TCONS_00024700 and
NR_028454. These lncRNAs can be detected in plasma and may
predict responsiveness of metastasis to radioiodine without
exposing patients to diagnostic isotope scan .
Recurrence risk of PTC after radioactive iodine (RAI) treatment is
around 15.6% in 3 years . These recurrent lesions are often
refractory to RAI treatment and 3 year overall survival rate is less
than 50%. Molecular targeted agents can be used in treatment of
such RAI refractory cases. A study by Xiang et al.  researched
into this possibility. Within this study, thyroid cancer cell lines
were exposed to sublethal dose of RAI. Microarray analysis of
pre-exposure and post-exposure cancer cell lines was performed
. SCL6A9 was shown to be significantly decreased in post
exposure cell lines. To further confirm the role of SCL6A9, radio
resistant cell lines were transfected with this gene. The result
was increased susceptibility of earlier radio resistant cells.
SCL6A9 was shown to act as a PARP1 promoter. While PARP1
acts as a DNA repair gene effectiveness of SCL6A9 was due to
ATP depletion following upregulation of PARP1 . Thus SCL6A9
may be a novel therapeutic agent in treatment of patients with
lncRNAs have been revolutionising the biology of cancer genetics.
Evidence is accumulating day by day regarding the role they
play in various aspects of cancer pathogenesis. Thyroid cancer
continues to have a very favourable prognosis in comparison
to others. However, few cases fail to respond to treatment
especially in cases of recurrence. lncRNA offer a way for better
understanding of the mechanism of resistance. In neat future
lncRNA based therapy could possibly bring these outliers towards
a favourable prognosis.
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