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Expression and significance analyses of microRNAs in colorectal cancer

  • Authors:
    • Jing Zhang
    • Liwei Sun
    • Changxiu Yan
    • Honggang Ran
    • Kaiyong Qu
    • Zhijian Chen
    • Argen Bahet
    • Chenxi Wang
    • Xin Cai
    • Guohong Zhuang
    • Zeyang Lin
  • View Affiliations / Copyright

    Affiliations: Department of Laboratory Medicine, Fujian Key Clinical Specialty of Laboratory Medicine, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian 361000, P.R. China, Organ Transplantation Institute of Xiamen University, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, Fujian 361000, P.R. China, School of Medicine, Xiamen University, Xiamen, Fujian 361000, P.R. China, Department of Pathology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361000, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 20
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    Published online on: February 5, 2026
       https://doi.org/10.3892/mco.2026.2929
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Abstract

MicroRNAs (miRNAs or miRs) serve as potential diagnostic and prognostic markers or therapeutic targets. However, their roles in the pathogenesis of colorectal cancer (CRC) is not fully understood. The aim of the present study was to investigate the expression levels and functions of miR‑205, miR‑376c, and miR‑539 in CRC development and prognosis. Multiple GEO databases were used to explore miRNA expression levels and associations in CRC cancer and adjacent/normal tissues. In addition, the associations between the expression of the miRNAs and the clinicopathological features of CRC were analyzed. The clinical data and specimens of 25 patients with CRC were collected, detected and analyzed. Combining bioinformatics analysis and databases, the relationship between the three miRNAs and CRC progression and prognosis was explored. In the GSE41655 dataset, miR‑376c, miR‑539, and miR‑205 were all downregulated in tumor tissues, with miRNA‑376c exhibiting the most pronounced downregulation. MiR‑376c was closely associated with CRC liver metastasis, especially in the synchronous metastasis condition. Additionally, in the miRDB database, an analysis of the overlapping predicted target genes for miR‑205, miR‑376c, and miR‑539 revealed that these three miRNAs share 53 common predicted target genes. Not only did miR‑539 and miR‑205 significantly differ according to tumor stage and lymph node metastasis, but also their upregulation was significant in tumor advanced stage and lymph node metastasis according to logistic regression in collected cancer tissues. Furthermore, miR‑205 was significantly upregulated in tumor differentiation according to logistic regression. In conclusion, miR‑205, miR‑376c, and miR‑539 were revealed to be involved in the development and prognosis of CRC and may be potential targets for CRC therapy.

View Figures

Figure 1

Overview of the study design and
analytical workflow. The study employed a research framework of
‘computer simulation analysis-experimental validation-integrated
interpretation’ to systematically investigate the expression
patterns, clinical significance, and potential mechanisms of
miR-205, miR-376c, and miR-539 in CRC. The flowchart clearly
illustrates the entire process including: Obtaining data from
public databases (GEO, UALCAN, miRBase, miRDB) for bioinformatics
mining, collecting 25 clinical sample pairs for qPCR validation,
and finally integrating analyses using statistical and
bioinformatics tools. Key findings include: All three miRNAs were
significantly downregulated in cancer tissues; miR-376c was
associated with liver metastasis (particularly synchronous
metastasis); miR-205 and miR-539 were associated with tumor
differentiation, staging, and lymph node metastasis, respectively;
target gene prediction revealed 53 common potential targets shared
among the three miRNAs, suggesting their potential involvement in
CRC progression through a synergistic regulatory network. This
integrated flowchart visually represents the overall study approach
from hypothesis validation to mechanistic exploration and
highlights its main conclusions. CRC, colorectal cancer; miRNA or
miR, microRNA.

Figure 2

Expression profiles and correlation
analysis of miR-205, miR-376c, and miR-539 in colorectal cancer and
non-cancerous tissues from the GSE41655 dataset. The expression
levels and correlation of miR-205, miR-376c and miR-539 in normal
tissues and colorectal cancer tissues were analyzed in the GSE41655
dataset, which contained 35 colorectal tumor tissues, 15 matched
adjacent tissues, and 57 colorectal adenoma tissues. (A) miR-205
expression. (B) miR-376c expression. (C) miR-539 expression. (D)
Correlation analysis of the expression of miR-205, miR-376 and
miR-539 in cancer tissues. N, normal tissues; A, adenoma tissues;
C, colorectal cancer tumor tissues. *P<0.05,
***P<0.001 and ****P<0.0001. miR,
microRNA; ns, not statistically significant.

Figure 3

Expression levels of miR-205,
miR-376c and miR-539 are significantly different between CRC
tissues and adjacent tissues, as assessed using RT-qPCR. (A)
Comparison of miR-205 expression levels in human CRC tissues and
matched adjacent tissues. (B) Comparison of miR-376c expression
levels in human CRC tissues and matched adjacent tissues. (C)
Comparison of miR-539 expression levels in human CRC tissues and
matched adjacent tissues. miRNA expression was quantified by
RT-qPCR and normalized to that in the matched adjacent normal
tissues. (D) Correlation analysis of the expression of miR-205,
miR-376 and miR-539 in tumor and normal tissues.
*P<0.05 and **P<0.01. miR, microRNA;
CRC, colorectal cancer; RT-qPCR, reverse transcription quatitative
PCR.

Figure 4

Relationship between the relative
expression levels of miR-205, miR-376c and miR-539, and the
presence or absence of liver metastasis in the GSE81581 dataset.
(A) Relationship between miR-205 expression and CRC liver
metastasis. (B) Relationship between miR-376c expression and CRC
liver metastasis. (C) Relationship between miR-539 expression and
CRC liver metastasis. (D) Relationship between miR-376c expression
and metachronous liver metastasis. (E) Relationship between
miR-376c expression and synchronous liver metastasis.
*P<0.05 and **P<0.01. miR, microRNA;
CRC, colorectal cancer; ns, not statistically significant.

Figure 5

Relationship between the relative
expression levels of miR-205, miR-376c and miR-539, and the
development of CRC. (A-C) The expression of miR-205, miR-376c and
miR-539 in healthy individuals and patients with CRC was analyzed
using UALCAN. (D-F) The expression of miR-205, miR-376c and miR-539
in COAD based on individual cancer stages was analyzed using
UALCAN. (G-I) The expression of miR-205, miR-376c and miR-539 in
COAD based on nodal metastatis status was analyzed using UALCAN.
(J-L) The effects of miR-205, miR-376c and miR-539 expression
levels on the survival of patients with COAD was analyzed using
UALCAN. miR, microRNA; CRC, colorectal cancer; COAD, colorectal
adenocarcinoma.

Figure 6

Sequences of miR-205, miR-376, and
miR-539 collected from the miRBase database, and predicted target
genes for miR-205, miR-376, and miR-539 mined from the miRDB
database for correlation analysis. (A) 5p and 3p mature sequences
of miR-205, miR-376c, and miR-539. (B) UpSet plot of the target
gene intersection analysis for the 5p and 3p mature sequences of
miR-205, miR-376, and miR-539. (C) Venn diagram of the target gene
intersection analysis for the 5p and 3p mature sequences of
miR-205, miR-376, and miR-539. miR, microRNA.
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Spandidos Publications style
Zhang J, Sun L, Yan C, Ran H, Qu K, Chen Z, Bahet A, Wang C, Cai X, Zhuang G, Zhuang G, et al: Expression and significance analyses of microRNAs in colorectal cancer. Mol Clin Oncol 24: 20, 2026.
APA
Zhang, J., Sun, L., Yan, C., Ran, H., Qu, K., Chen, Z. ... Lin, Z. (2026). Expression and significance analyses of microRNAs in colorectal cancer. Molecular and Clinical Oncology, 24, 20. https://doi.org/10.3892/mco.2026.2929
MLA
Zhang, J., Sun, L., Yan, C., Ran, H., Qu, K., Chen, Z., Bahet, A., Wang, C., Cai, X., Zhuang, G., Lin, Z."Expression and significance analyses of microRNAs in colorectal cancer". Molecular and Clinical Oncology 24.3 (2026): 20.
Chicago
Zhang, J., Sun, L., Yan, C., Ran, H., Qu, K., Chen, Z., Bahet, A., Wang, C., Cai, X., Zhuang, G., Lin, Z."Expression and significance analyses of microRNAs in colorectal cancer". Molecular and Clinical Oncology 24, no. 3 (2026): 20. https://doi.org/10.3892/mco.2026.2929
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang J, Sun L, Yan C, Ran H, Qu K, Chen Z, Bahet A, Wang C, Cai X, Zhuang G, Zhuang G, et al: Expression and significance analyses of microRNAs in colorectal cancer. Mol Clin Oncol 24: 20, 2026.
APA
Zhang, J., Sun, L., Yan, C., Ran, H., Qu, K., Chen, Z. ... Lin, Z. (2026). Expression and significance analyses of microRNAs in colorectal cancer. Molecular and Clinical Oncology, 24, 20. https://doi.org/10.3892/mco.2026.2929
MLA
Zhang, J., Sun, L., Yan, C., Ran, H., Qu, K., Chen, Z., Bahet, A., Wang, C., Cai, X., Zhuang, G., Lin, Z."Expression and significance analyses of microRNAs in colorectal cancer". Molecular and Clinical Oncology 24.3 (2026): 20.
Chicago
Zhang, J., Sun, L., Yan, C., Ran, H., Qu, K., Chen, Z., Bahet, A., Wang, C., Cai, X., Zhuang, G., Lin, Z."Expression and significance analyses of microRNAs in colorectal cancer". Molecular and Clinical Oncology 24, no. 3 (2026): 20. https://doi.org/10.3892/mco.2026.2929
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