Introduction
CRC is one of the most common cancers and ranks
as the second leading cause of cancer-related deaths
worldwide.[] While CRC has historically been more
common in individuals aged 50 and older, the incidence
of early-onset CRC has been rising in both males and females.
This shift in age distribution suggests that younger adults may be increasingly exposed to potential risk
factors, leading to various genetic alterations.[,] CRC
develops through a multistep process, beginning with
the transformation of normal colorectal epithelium into
an adenoma, and eventually progressing into an invasive
and metastatic tumor.[] Tumor suppressor genes
(TSGs) play a crucial role in regulating key cellular
functions, including DNA replication, repair, and transcription during cell division.[] The loss of function in
TSGs is a common mechanism that drives the initiation
and progression of CRC.[] ARID1A has emerged as a
significant tumor suppressor, regulating the expression
of multiple genes involved in cell division, DNA damage
repair, and apoptosis.[,] It is typically expressed at low
levels throughout the cell cycle and is degraded during
mitosis, but it accumulates during the G0/G1 phase to
induce cell cycle arrest.[,] Recent studies have revealed
that ARID1A influences cancer-related signaling
pathways by regulating the transcriptional activities of
various proteins and nuclear hormone receptors.[]
Mutations and genetic variants are key hallmarks
of cancer, playing a pivotal role in cancer initiation
and progression.[] In 2010, two studies using nextgeneration
sequencing revealed a high frequency of
inactivating ARID1A variants in highly aggressive
ovarian cancers, prompting further investigation into
its function as a tumor suppressor gene across various
cancers.[,] More than 97% of cancer-related
ARID1A variants are inactivating, often resulting from
nonsense or frameshift mutations that lead to partial or
complete loss of functional ARID1A protein.[] Most
cancer-associated ARID1A variants are heterozygous
and correlate with reduced protein expression, suggesting
that haploinsufficiency may contribute to cancer
development.[] The reduction or loss of ARID1A
expression has been linked to tumorigenesis in a wide
range of cancers, including gastrointestinal carcinoma.
[] Significant efforts have been made to identify molecular
markers that enable personalized therapeutic
strategies to improve disease diagnosis and treatment.
Recently, there has been growing interest in developing
cancer therapies tailored to the ARID1A variant status.
This study aims to explore the spectrum of ARID1A
mutations in exon 9 and their expression in colorectal
cancer (CRC). We shall also examine the potential relationship
between decreased ARID1A expression and
various clinicopathological characteristics.
Methods
This study received approval from the Institutional
Ethics Committee of Government Medical College Srinagar
(No: 66/ETH/GMC, Date: 30/03/2017) and conducted
according to the Declaration of Helsinki.
Study Design
This cross-sectional study was conducted by the Department
of Biochemistry and General Surgery, Shri
Maharaja Hari Singh and Super Specialty Hospital, associated with Government Medical College Srinagar,
North India.
Study Subjects and Sample Collection
The study included eighty-six (n=87) histopathologically
diagnosed CRC patients.
Inclusion and Exclusion Criteria
All enrolled patients were newly diagnosed cases, and
none had undergone chemotherapy or radiation. The
individuals did not have any genetic disorder
Sample Collection
Colorectal tumor tissue samples and their neighboring
normal tissue was taken from each CRC patient being
operated upon in the Department of Surgery, Shri Maharaja
Hari Singh (SMHS) and Superspeciality Hospital,
Srinagar. The patients' clinicopathological data was
supplied by the Medical Record Department. One aliquot
of each tissue sample was immediately stored in
RNA-later (Sigma-Aldrich, USA) at 4°C overnight to
achieve full solution penetration before being frozen at
-80°C for RNA extraction. Another aliquot was frozen
immediately and kept at -80°C for DNA analysis.
DNA Isolation
Genomic DNA was extracted from tissue samples using
the QIAamp DNA Mini Kit (Qiagen, Germany) in
accordance with the protocol. The purity of the isolated
DNA was validated using 1% agarose gel electrophoresis.
The purity and concentration were evaluated using
the NanoDrop 2000c spectrophotometer (Thermo Scientific,
USA). DNA samples with high molecular mass,
little fragmentation or shearing, and an A260/280 ratio
of 1.7-1.9 were employed for molecular analysis.
Polymerase Chain Reaction (PCR)
The primers used to amplify the exon-9 of ARID1A
gene were: Forward 5´-CACAGCACTATTTGGCTCCAG-
3´; reverse 5´-ATCATCTCTGGGCTGGCTG-3´
(Eurofins Genomics, Germany). The PCR reaction
was performed in 50µl of reaction mixture containing
12.5µl of 2X PCR master mix (3B BlackBio, Biotech,
India), 50-150 ng of genomic DNA, and 0.2 mM of
each primer. The reaction cycle included an initial denaturation
at 94°C for 5 minutes, followed by 35 cycles
of denaturation at 94°C for 20 sec, annealing at 58°C
for 30 sec, extension at 72°C for 30 sec, with a final extension
at 72°C for 7 minutes. The 343 bp PCR product
was run on 2.5% agarose gel and visualized using
Omega Lum G Gel Documentation System (Aplegen).
DNA Sequencing
The PCR products were sequenced using the ABI
prism 310 automated DNA sequencer (ThermoFisher
Scientific, USA) using the Sangar dideoxy technique.
RNa Isolation Followed by cDNA Synthesis
Total RNA was extracted from tissue samples using
the TRIzol reagent (ThermoFisher Scientific, USA)
and quantified. The RNA purity and concentration
were determined using a NanoDrop 2000c spectrophotometer
(ThermoScientific, USA), and an A260/
A280 ratio of 1.8-2.0 was judged suitable for further
analysis. A 1.5% agarose gel revealed the presence of
28S, 18S, and 5S rRNA bands, confirming RNA integrity.
cDNA was produced using the RevertAid First
Strand cDNA Synthesis Kit (ThermoFisher Scientific,
USA) according to the manufacturer"s instructions,
with the reactions incubated at 37°C for 60 minutes,
followed by 10 minutes at 95°C.
Quantitative real-time PCR for (qRT-PCR) for
relative mRNA expression of ARID1A
The relative mRNA expression of ARID1A in colorectal
tumor tissue samples and their adjacent normal
tissues was measured by using qRT PCR (7500 Real-
Time PCR system (ThermoFisher Scientific, USA).
Each sample was analyzed in triplicate and expression
levels were normalized using GAPDH as an internal
control. The primers used were as follows: Forward
5´-CTTCAACCTCAGTCAGCTCCCA-3´ reverse:
5´GGTCACCCACCTCATACTCCTTT-3´; and GAPDH
forward 5´-TTTGGCTACAGCAACAGGGT-3´
and GAPDH reverse 5´-TCCTCTTGTGCTCTTGCTGG-
3´. The PCR reaction mixture consists of 10µl
of KAPA SYBR®FAST master mix (Sigma-Aldrich,
USA), 0.4µl of cDNA from each sample, 0.2µM of each
forward and reverse primers, in a total volume of 20µl.
The PCR condition included an initial 10-minute preheat
at 95°C, followed by 40 cycles of denaturation at
95°C for 30 sec, annealing at 60°C for 1 minute, extension
at 72°C for 35 sec, and a final extension at 72°C for
10 minutes. Specificity of the PCR was confirmed using
melting curve analysis (58-95°C). ARID1A mRNA was
quantified based on the cycle threshold (Ct) value. Relative
expression was calculated using the 2-ΔΔCt method.
[] The fold change in expression between tumor and
adjacent normal tissue was determined as 2-ΔΔCt.
Statistical Analysis
The data was analyzed using SPSS software version 23.0
(SPSS Inc., Chicago, IL, USA). Continuous variables
were analyzed using independent and paired t-tests, whilst categorical/dichotomous variables were tested
using Pearson's χ2 test, Fisher's exact test, or χ2 test. Logistic
regression was used to compute odds ratios (ORs)
and 95% confidence intervals (CIs). Statistical significance
was assessed using a two-sided p-value<0.05.
Results
Patient Characteristics
In this study, histologically confirmed colorectal
cancer (CRC) cases (n=87) and their adjacent normal
tissues were analyzed for ARID1A variants and
mRNA expression. The mean age of CRC patients was
52.7±12.2 years. CRC was more prevalent in males
(64.3%) than in females (35.6%). Notably, 56.3% of patients had BMI out of the normal range. 15.5% of
CRC patients had a positive family history of gastrointestinal
cancer. Table 1 provides a detailed breakdown
of the socio-demographic and clinicopathological
characteristics of enrolled CRC cases.
Table 1. Demographic and clinicopathological parameters
of the study subjects
Analysis of ARID1A Variants
The CRC samples were screened for the presence of
ARID1A variants at exon-9 of the ARID1A gene. Partial
electrophoretograms (forward) of ARID1A exon-9
in CRC patients is shown in Figure 1 (a-d). The detected
variants were present in 17 cases (19.5%). Out of 17 cases, 9 (53.0%) were mutually exclusive (only
one variant) whereas, 6 (35.3%) harboured at least two
variants and 2 (11.7%) of them carried three variants.
The heterozygous condition was predominant. The
nonsynonymous variants were rare than synonymous
type (Table 2). The high frequency of variants (70.3%)
was observed in the age group of ≥50 years.
Fig. 1. Partial electrophoretograms (forward) of ARID1A variations at exon-9 in CRC patients,
demonstrating changed sequences. (a) Electrophoretogram of the C-to-A
substitution (proline to histidine) at amino acid position 916. (b) Electrophoretogram
demonstrating a T-to-A substitution at amino acid position 934. (c) Electrophoretogram
revealing the C-to-A substitution at amino acid position 955. (d)Electrophoretogram
demonstrating a T-to-A substitution at amino acid position 958.
Table 2. ARID1A variants at exon-9 of colorectal tumor tissue samples
In Silico Analysis of Pro916His
The nonsynonymous missense Pro916His was submitted
to SIFT and PROVEN computational tools
to predict the effect of amino acid substitution on protein function. Both software tool predicted the
deleterious effect with the Sift score of ≤0.05 and
PROVEN score of -3.839. The disease-associated impact
of histidine substitution was analyzed by Mut-
Pred2 & GO software. The amino acid substitution
was predicted as neutral by both tools (score>0.5).
I-mutant 2.0 and MU pro were used to examine the
effect of ARID1A variant on the structural stability
of proteins. I-mutant 2.0 detected decreased protein
stability with reliability index 5, whereas the MU pro
predicted decreased protein stability with ΔΔG=-0.5.
Furthermore, to study the effect of the variant on
protein structure, the Hope project revealed substitution
of proline to histidine disturbs the backbone
conformation of the resultant protein.
Relative mRNA Expression of ARID1A Gene
We used qRT-PCR to examine the expression of ARID1A
mRNA in 87 CRC tumor tissues and surrounding
normal tissue samples. Among the 87 CRC patients,
17.2% (15/87) exhibited under-expression of ARID1A mRNA compared to adjacent normal tissues. The average
fold change (2-ΔΔCt) found to be 0.70 exhibited a
statistically significant decrease of 1.43-fold (1/0.70) in
mRNA levels of the ARID1A gene (Table 3).
Table 3. Comparison of mRNA expression of ARID1A gene between CRC tumor tissues and adjacent normal tissue
Figure 2 shows a box and whisker plot of relative
mRNA expression. The melt curve studies revealed no
production of any non-specific product. Table 4 shows
the association between ARID1A expression and other
clinicopathological characteristics. The data revealed
that there was no significant association between the
decreased mRNA expression of the ARID1A with any
of the socio-demographic and clinicopathological
characteristics of CRC cases (p>0.05).
Fig. 2. A box and whisker plot demonstrating ARID1A
mRNA expression in CRC patients and controls
(adjacent normal). The experiment was carried
out in triplets. Colorectal tumor tissue samples
showed considerably lower mRNA expression
of ARID1A compared to non-tumorous tissues
(p<0.001). Data was given as mean±SD.
Table 4. Correlation between ARID1A expression and clinicopathological variables of CRC
Discussion
CRC is one of the leading causes of cancer-related mortality
in the world. The global trends of CRC are also
heterogeneous, as it is manifested in differences in incidence
and mortality rates influenced by factors such
as age, gender, and ethnicity.[]
The underlying molecular mechanism of CRC is
driven by the continuous acquisition of genetic and
environmental risk factors, related to the suppression
of tumor suppressor genes (TSGs).[] ARID1A has
emerged as a potent TSG due to its association with various
types of cancer, including CRC.[] ARID1A is an
important subunit of the SWI/SNF chromatin remodelling
complex, which plays a pivotal role in regulating
gene expression and maintaining cellular homeostasis.
Therefore, ARID1A is essential for a broad spectrum
of cellular processes including proliferation, differentiation,
DNA damage repair, and genomic stability.[]
Genetic variations leading to altered gene expression,
disrupt these processes resulting in uncontrolled cell
division and tumor formation.[] Several studies have
demonstrated that genetic variations in ARID1A often
leads to haploinsufficiency in various types of cancers,
which are linked to more aggressive characteristics and
poor clinical outcome.[] In the present study, we
identified that 19.5% of the patients have variations in
the ARID1A gene. This prevalence emphasizes the role of ARID1A in the molecular context of CRC. Majority
of these variations were heterozygous as it was expected
because earlier studies suggested that the haploinsufficiency
of ARID1A is sufficient to cause tumorigenesis
by disrupting normal chromatin remodelling structure
and gene expression.[] Therefore, ARID1A haploinsufficiency
is associated with increased genomic instability.
The Pro916His variation was predicted to be
deleterious by the in-silico tools because it is a nonsynonymous
missense variant that may affect the protein
function and stability. This variation was demonstrated
to change the protein's secondary structure which could alter the protein"s ability to correctly interact with
the SWI/SNF complex possibly causing abnormal cell
division and defective DNA repair mechanism.
Furthermore, according to the published data the
loss or low expression of ARID1A has a significant role
in the development and progression of CRC.[] The
reduced ARID1A could alter the antigen presentation of
tumor, potentially leading to strong immune response
in CRC. However, this can also prompt the tumor to
develop mechanism to evade immune detection.[]
Spontaneous or mutation-induced reduction in
ARID1A expression can act as a tumorigenic trigger, contributing to both the initiation and progression of
cancer. ARID1A serves a dual role: As a "gatekeeper"
controlling cell proliferation, and as a "caretaker" tumour
suppressor that preserves genomic integrity by
preventing sequence mutations and chromosomal aberrations.[] Studies by Wei et al.[] and Erfani et
al.[] have demonstrated that decreased or lost ARID1A
expression is significantly associated with distant
metastasis, lymph node invasion, and consequently,
poor prognosis in CRC.
Although statistically insignificant, the frequency
of CRC among older individuals (≥50 years) was
higher compared to younger individuals. The CRC
risk increases significantly with age due to the combined
effects of several risk factors, with over 70% of
CRC patients being over 55 years old.[] Nevertheless,
early exposure to many of the recognized risk factors
increases the likelihood of developing early-onset of
CRC (EOCRC), which is a considerable cancer concern
among young individuals.[,] The causes of
EOCRC are not yet fully understood; however, factors
such obesity, physical inactivity and diet have been
linked to its development.[]
Obesity is a well-established risk factor for colorectal
cancer across all age groups. Elevated BMI, especially
abdominal obesity, is closely associated with chronic
low-grade inflammation and insulin resistance, both of
which may contribute to the formation of neoplastic
lesions in colorectal tissue.[] In line with these findings,
our study observed a higher incidence of CRC in
patients with abnormal BMI compared to the control
group, although the difference was not statistically significant
(p<0.001).
As per previous studies, the significant loss of
ARID1A expression in CRC patients has been recorded
compared to controls.[,] Consistent with
the above studies, Quantitative real-time PCR (qRTPCR)
analysis revealed significant under-expression
of ARID1A mRNA in 17.2% of the CRC cases compared
to adjacent normal tissues. This reduction in
mRNA levels indicates a potential loss of functional
protein, corroborating the variational analysis. The
fold change analysis exhibited a 1.43-fold decrease
in ARID1A expression, suggesting that even partial
loss of ARID1A function can contribute to CRC
pathogenesis. Several studies have reported that the
ARID1A variations and reduced expression levels
were significantly correlated with tumor histological
grade, advanced tumor depth, poor differentiation,
lymphatic metastasis, primary tumor location and
early tumor stage.[] Notably, the study failed to establish any correlation of ARID1A mRNA expression
with clinicopathological characteristics such as
age, gender, and tumour stage. This fact indicates that
ARID1A variation and altered expression can be involved
in CRC development without consideration of
other characteristics of patients.
The discovery of the presence of ARID1A variations
and their effects on the function of the protein provides
new possibilities of targeted treatment of CRC. Understanding
the link between the ARID1A loss and immune
activation can help to shape the development of
effective therapies, such as tumors with different ARID1A
variations might respond differently to the immunotherapies
such as checkpoint inhibitors. By targeting
the altered immune pathways or harnessing the increased
immune activation found in ARID1A-deficient
tumors, novel treatment approach can be developed to
boost anti-tumor immunity and improve patient outcome.
Furthermore, therapies that can either reverse
the loss of ARID1A function or at least supply for it
might be new treatment strategies for CRC patients. For
example, drugs that act on epigenetic changes or those
that boost DNA repair mechanisms could be used in
combination with the ARID1A status to enhance the effectiveness
of the treatment. The results obtained are in
line with the prior literature that has established the involvement
of ARID1A in several cancers such as ovarian,
gastric, and endometrial cancers.[]
Limitation of the Study
Considerable number of patients in this region were
diagnosed with advanced stage CRC and were in-operable.
For that reason, the tumor tissue could not be
collected from those very patients. Therefore, studies
are warranted to validate the results, especially in case
of CRC, due to relatively modest sample size.
Conclusion
In conclusion, the present study confirmed a high frequency
of ARID1A variations and down-regulation of
ARID1A protein in CRC tissues compared to the normal
adjacent tissues. Our research has shown that ARID1A
plays a significant role in colorectal tumorigenesis
and may be used as a biomarker for CRC. Subsequent
research with more participants and deeper assessment
of the ARID1A-associated molecular processes
are required to enhance the understanding of the gene's
function in CRC and to evaluate the possibility of using
it as a biomarker for individualized treatment.
Ethics Committee Approval: The study was approved by
the Institutional Ethics Committee of Government Medical
College Srinagar (no: 66/ETH/GMC, date: 30/03/2017).
Informed Consent: Informed consent was obtained from
all participants.
Conflict of Interest Statement: The authors have no conflicts
of interest to declare.
Funding: The study was funded by the Department of Biochemistry,
Govt. Medical College Srinagar and Associated
Hospitals, 190010, J&K, India.
Use of AI for Writing Assistance: No AI technologies utilized.
Author Contributions: Conception: J.Q., M.S.K.; Design:
J.Q.; Supervision: S.M., M.D.W.; Fundings: S.M.; Materials:
S.M.; Data Collection and/or Processing: J.Q., M.S.K., S.S.L.;
Analysis and/or interpretation: M.S.K.; Literature Review:
J.Q.; Writer: M.S.K., J.Q.; Critical Review: M.S.K.
Acknowledgments: The authors express their gratitude for
the valuable efforts undertaken by the research team in this
research.
Peer-review: Externally peer-reviewed.
References
Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A.
Colorectal cancer statistics, 2023. CA Cancer J Clin
2023;73(3):233-54.
Adigun AO, Adebile TM, Okoye C, Ogundipe TI,
Ajekigbe OR, Mbaezue RN, et al. Causes and prevention
of early-onset colorectal cancer. Cureus
2023;15(9):e45095.
Akimoto N, Ugai T, Zhong R, Hamada T, Fujiyoshi K,
Giannakis M, et al. Rising incidence of early-onset colorectal
cancer ? A call to action. Nat Rev Clin Oncol
2021;18(4):230-43.
Armaghany T, Wilson JD, Chu Q, Mills G. Genetic alterations
in colorectal cancer. Gastrointest Cancer Res
2012;5(1):19-27.
Abreu Velez AM, Howard MS. Tumor-suppressor
genes, cell cycle regulatory checkpoints, and the skin.
N Am J Med Sci 2015;7(5):176-88.
Malki A, ElRuz RA, Gupta I, Allouch A, Vranic S, Al
Moustafa AE. Molecular mechanisms of colon cancer
progression and metastasis: Recent insights and advancements.
Int J Mol Sci 2020;22(1):130.
Mandal J, Mandal P, Wang TL, Shih IM. Treating
ARID1A mutated cancers by harnessing synthetic
lethality and DNA damage response. J Biomed Sci
2022;29(1):71.
Xu S, Tang C. The role of ARID1A in tumors: Tumor
initiation or tumor suppression? Front Oncol
2021;11:745187.
De P, Dey N. Mutation-driven signals of ARID1A and
PI3K pathways in ovarian carcinomas: Alteration is an
opportunity. Int J Mol Sci 2019;20(22):5732.
Qadir J, Majid S, Khan MS, Rashid F, Wani MD, Bhat
SA. Implication of ARID1A undercurrents and PDL1,
TP53 overexpression in advanced gastric cancer.
Pathol Oncol Res 2021;27:1609826.
Odnokoz O, Wavelet-Vermuse C, Hophan SL, Bulun
S, Wan Y. ARID1 proteins: From transcriptional and
post-translational regulation to carcinogenesis and
potential therapeutics. Epigenomics 2021;13(10):809-23.
Tufail M, Hu JJ, Liang J, He CY, Wan WD, Huang
YQ, et al. Hallmarks of cancer resistance. iScience
2024;27(6):109979.
Jones S, Wang TL, Shih Ie M, Mao TL, Nakayama K,
Roden R, et al. Frequent mutations of chromatin remodeling
gene ARID1A in ovarian clear cell carcinoma.
Science 2010;330:228-31.
Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse
K, Zeng T, et al. ARID1A mutations in endometriosis-
associated ovarian carcinomas. N Engl J Med
2010;363:1532-43.
Wu JN, Roberts CW. ARID1A mutations in cancer:
Another epigenetic tumor suppressor? Cancer Discov
2013;3(1):35-43.
Fontana B, Gallerani G, Salamon I, Pace I, Roncarati
R, Ferracin M. ARID1A in cancer: Friend or foe?
Front Oncol 2023;13:1136248.
Lu S, Duan R, Cong L, Song Y. The effects of ARID1A
mutation in gastric cancer and its significance for
treatment. Cancer Cell Int 2023;23(1):296.
Livak KJ, Schmittgen TD. Analysis of relative gene
expression data using real-time quantitative PCR
and the 2(-Delta Delta C(T)) method. Methods
2001;25(4):402-8.
Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal
cancer: Incidence, mortality, survival, and risk
factors. Prz Gastroenterol 2019;14(2):89-103.
Kamori T, Oki E, Shimada Y, Hu Q, Hisamatsu Y, Ando
K, et al. The effects of ARID1A mutations on colorectal
cancer and associations with PD-L1 expression by
stromal cells. Cancer Rep Hoboken 2022;5(1):e1420.
Zou J, Qin W, Yang L, Wang L, Wang Y, Shen J, et al.
Genetic alterations and expression characteristics of
ARID1A impact tumor immune contexture and survival
in early-onset gastric cancer. Am J Cancer Res
2020;10(11):3947-72.
Soto-Castillo JJ, Llavata-Marti L, Fort-Culillas R,
Andreu-Cobo P, Moreno R, Codony C, et al. SWI/
SNF complex alterations in tumors with rhabdoid
features: Novel therapeutic approaches and opportunities
for adoptive cell therapy. Int J Mol Sci
2023;24(13):11143.
Lebedev T, Kousar R, Patrick B, Usama M, Lee MK,
Tan M, et al. Targeting ARID1A-deficient cancers: An
immune-metabolic perspective. Cells 2023;12(6):952.
Wei XL, Wang DS, Xi SY, Wu WJ, Chen DL, Zeng
ZL, et al. Clinicopathologic and prognostic relevance
of ARID1A protein loss in colorectal cancer. World J
Gastroenterol 2014;20:18404-12.
Erfani M, Hosseini SV, Mokhtari M, Zamani M, Tahmasebi
K, Alizadeh N, et al. Altered ARID1A expression
in colorectal cancer. BMC Cancer 2020;20(1):350.
Sifaki-Pistolla D, Poimenaki V, Fotopoulou I, Saloustros
E, Mavroudis D, Vamvakas L, et al. Significant
rise of colorectal cancer incidence in younger adults
and strong determinants: 30 years longitudinal differences
between under and over 50s. Cancers Basel
2022;14(19):4799.
Rychter AM, Lykowska-Szuber L, Zawada A, Szymczak-
Tomczak A, Ratajczak AE, Skoracka K, et al. Why
does obesity as an inflammatory condition predispose
to colorectal cancer? J Clin Med 2023;12(7):2451.
Wanna Udom S, Aluksanasuwan S, Somsuan K,
Mongkolwat W, Sakulsak N. ARID1A overexpression
inhibits colorectal cancer cell migration through the
regulation of epithelial mesenchymal transition. Mol
Med Rep 2024;30:201.
Zhao S, Wu W, Jiang Z, Tang F, Ding L, Xu W, et al.
Roles of ARID1A variations in colorectal cancer: A
collaborative review. Mol Med 2022;28(1):42.
