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BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Colorectal Cancer | Research

The diagnostic potential of miR-196a-1 in colorectal cancer

Authors: Bayan Mehrjoei, Lida Haghnazari, Homayoon Bashiri, Nayebali Rezvani

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

Colorectal cancer (CRC) is a common malignancy worldwide. MicroRNAs (miRNAs) are important epigenetic alterations that notably impact various physiological and pathological processes by acting as negative regulators of gene expression. Furthermore, they have a vital function in different types of cancers, including CRC. In this research, we evaluated, for the very first time, the expression levels of miR-196a-1 in the tissue and plasma of patients with CRC and also homeobox D8 (HOXD8) as the target gene.

Materials and methods

This study included a collection of 220 plasma and tissue samples from 55 patients diagnosed with CRC, as well as 55 healthy individuals matched by age and sex. Total RNA was extracted from plasma and tissue samples, and then polyadenylation and cDNA synthesis were performed. The expression levels of miR-196a-1 and HOXD8 as target gene was evaluated by quantitative RT-PCR (qRT-PCR) assay. We compared the diagnostic value of plasma miR-196a-1 with that of the circulating tumor markers CA19-9 and CEA using a Receiver Operating Characteristics (ROC) analysis. The association of miR-196a-1 with clinicopathological characteristics was assessed in tissue and plasma samples from patients with CRC.

Results

Our data demonstrated that the expression levels of miR-196a-1 in the tissue and plasma samples of CRC patients were 11.426- and 11.655-fold higher, respectively than those in adjacent normal tissue and plasma samples from normal subjects (p < 0.001). Through ROC curve analysis, it was identified that the sensitivity and specificity of miR-196a-1 for tissue samples, with an AUC of 0.925, were 89% and 98%, respectively. In addition, the sensitivity and specificity for plasma samples with an AUC of 0.801 were 70% and 98%, respectively. These findings reveal that miR-196a-1 is a useful biomarker for discriminating cases from controls. Furthermore, the expression of HOXD8 was not significantly altered in tumor tissue samples compared to adjacent normal tissues (P > 0.05).

Conclusions

These results show that miR-196a-1 has an oncogenic impact and plays a significant role in CRC development. The results also indicate that miR-196a-1 could serve as a novel noninvasive biomarker for the detection of CRC.
Literature
1.
Yoshikawa Y, Fukunaga M, Takahashi J, Shimizu D, Masuda T, Mizushima T, et al. Identification of the minimum combination of serum microRNAs to predict the recurrence of colorectal cancer cases. Ann Surg Oncol. 2023;30(1):233–43.CrossRefPubMed
2.
Dong J, Geng J, Tan W. MiR-363-3p suppresses tumor growth and metastasis of colorectal cancer via targeting SphK2. Biomed Pharmacother. 2018;105:922–31.CrossRefPubMed
3.
Rahimi F, Rezayatmand R, Shojaeenejad J, Tabesh E, Ravankhah Z, Adibi P. Costs and outcomes of colorectal cancer screening program in Isfahan, Iran. BMC Health Serv Res. 2023;23(1):13.CrossRefPubMedPubMedCentral
4.
Nejad ET, Moslemi E, Souni F, Mahmoodi M, Vali M, Vatanpour M, et al. The association between pro-vegetarian dietary pattern and risk of colorectal cancer: a matched case-control study. BMC Res Notes. 2023;16(1):326.CrossRefPubMedPubMedCentral
5.
Wang X, Chen L, Jin H, Wang S, Zhang Y, Tang X et al. Screening miRNAs for early diagnosis of colorectal cancer by small RNA deep sequencing and evaluation in a Chinese patient population. OncoTargets and Therapy. 2016:1159–66.
6.
Zhu D, Sun Y, Zhang D, Dong M, Jiang G, Zhang X, et al. miR–1 inhibits the progression of colon cancer by regulating the expression of vascular endothelial growth factor. Oncol Rep. 2018;40(2):589–98.PubMedPubMedCentral
7.
Amankwatia E, Chakravarty P, Carey F, Weidlich S, Steele R, Munro A, et al. MicroRNA-224 is associated with colorectal cancer progression and response to 5-fluorouracil-based chemotherapy by KRAS-dependent and-independent mechanisms. Br J Cancer. 2015;112(9):1480–90.CrossRefPubMedPubMedCentral
8.
Ling H, Pickard K, Ivan C, Isella C, Ikuo M, Mitter R, et al. The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis. Gut. 2016;65(6):977–89.CrossRefPubMed
9.
Niu L, Yang W, Duan L, Wang X, Li Y, Xu C, et al. Biological implications and clinical potential of metastasis-related miRNA in colorectal cancer. Mol Therapy-Nucleic Acids. 2021;23:42–54.CrossRef
10.
Hu X-X, Xu X-N, He B-S, Sun H-L, Xu T, Liu X-X, et al. microRNA-485-5p functions as a tumor suppressor in colorectal cancer cells by targeting CD147. J Cancer. 2018;9(15):2603.CrossRefPubMedPubMedCentral
11.
To KK, Tong CW, Wu M, Cho WC. MicroRNAs in the prognosis and therapy of colorectal cancer: from bench to bedside. World J Gastroenterol. 2018;24(27):2949.CrossRefPubMedPubMedCentral
12.
Guo Q, Qin H, Liu X, Zhang X, Chen Z, Qin T, et al. The emerging roles of human gut microbiota in gastrointestinal cancer. Front Immunol. 2022;13:915047.CrossRefPubMedPubMedCentral
13.
Fantini S, Salsi V, Vitobello A, Rijli FM, Zappavigna V. MicroRNA-196b is transcribed from an autonomous promoter and is directly regulated by Cdx2 and by posterior hox proteins during embryogenesis. Biochim et Biophys Acta (BBA)-Gene Regul Mech. 2015;1849(8):1066–80.CrossRef
14.
Lu Y-C, Chang JT, Chan E-C, Chao Y-K, Yeh T-S, Chen J-S, et al. miR-196, an emerging cancer biomarker for digestive tract cancers. J Cancer. 2016;7(6):650.CrossRefPubMedPubMedCentral
15.
Mo J-S, Park Y-R, Chae S-C. MicroRNA 196B regulates HOXA5, HOXB6 and GLTP expression levels in colorectal cancer cells. Pathol Oncol Res. 2019;25:953–9.CrossRefPubMed
16.
Pourdavoud P, Pakzad B, Mosallaei M, Saadatian Z, Esmaeilzadeh E, Alimolaie A, et al. MiR-196: emerging of a new potential therapeutic target and biomarker in colorectal cancer. Mol Biol Rep. 2020;47:9913–20.CrossRefPubMed
17.
Bhatlekar S, Fields JZ, Boman BM. Role of HOX genes in stem cell differentiation and cancer. Stem cells international. 2018;2018.
18.
Jin X, Dai L, Ma Y, Wang J, Yan H, Jin Y, et al. Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis. BMC Cancer. 2020;20(1):1–17.CrossRef
19.
Martinou E, Falgari G, Bagwan I, Angelidi AM. A systematic review on HOX genes as potential biomarkers in colorectal cancer: an emerging role of HOXB9. Int J Mol Sci. 2021;22(24):13429.CrossRefPubMedPubMedCentral
20.
Feng Y, Wang J, He Y, Zhang H, Jiang M, Cao D, et al. HOXD8/DIAPH2-AS1 epigenetically regulates PAX3 and impairs HTR-8/SVneo cell function under hypoxia. Biosci Rep. 2019;39(1):BSR20182022.CrossRefPubMedPubMedCentral
21.
Mansour MA, Senga T. HOXD8 exerts a tumor-suppressing role in colorectal cancer as an apoptotic inducer. Int J Biochem Cell Biol. 2017;88:1–13.CrossRefPubMed
22.
Sun S, Wang N, Sun Z, Wang X, Cui H. MiR-5692a promotes proliferation and inhibits apoptosis by targeting HOXD8 in hepatocellular carcinoma. J BUON. 2019;24(1):178–86.PubMed
23.
Debernardi S, Skoulakis S, Molloy G, Chaplin T, Dixon-McIver A, Young B. MicroRNA miR-181a correlates with morphological sub-class of acute myeloid leukaemia and the expression of its target genes in global genome-wide analysis. Leukemia. 2007;21(5):912–6.CrossRefPubMed
24.
Feng C, She J, Chen X, Zhang Q, Zhang X, Wang Y, et al. Exosomal miR-196a-1 promotes gastric cancer cell invasion and metastasis by targeting SFRP1. Nanomedicine. 2019;14(19):2579–93.CrossRefPubMed
25.
Yang H, Wang Y. Five miRNAs considered as molecular targets for predicting neuroglioma. Tumor Biology. 2016;37:1051–9.CrossRefPubMed
26.
Schimanski CC, Frerichs K, Rahman F, Berger M, Lang H, Galle PR, et al. High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells. World J Gastroenterology: WJG. 2009;15(17):2089.CrossRefPubMedCentral
27.
Okugawa Y, Grady WM, Goel A. Epigenetic alterations in colorectal cancer: emerging biomarkers. Gastroenterology. 2015;149(5):1204–25. e12.CrossRefPubMed
28.
Yuan D, Li K, Zhu K, Yan R, Dang C. Plasma miR-183 predicts recurrence and prognosis in patients with colorectal cancer. Cancer Biol Ther. 2015;16(2):268–75.CrossRefPubMedPubMedCentral
29.
Wen X, Chen Y, Fang X. Overexpression of HOXD8 inhibits the proliferation, migration and invasion of breast cancer cells by downregulating ILP2 expression. Experimental and Therapeutic Medicine. 2021;22(3):1–9.CrossRef
30.
Yao L, Ye P-C, Tan W, Luo Y-J, Xiang W-P, Liu Z-L, et al. Decreased expression of the long non-coding RNA HOXD-AS2 promotes gastric cancer progression by targeting HOXD8 and activating PI3K/Akt signaling pathway. World J Gastrointest Oncol. 2020;12(11):1237.CrossRefPubMedPubMedCentral
31.
Liu J, Li J, Su Y, Ma Z, Yu S, Meng X. CircTMEM59 serves as mir-410-3p sponge to inhibit the proliferation and metastasis of colorectal cancer by regulating HOXD8. Biochem Genet. 2022;60(6):2399–415.CrossRefPubMed
32.
Kanai M, Hamada J-I, Takada M, Asano T, Murakawa K, Takahashi Y, et al. Aberrant expressions of HOX genes in colorectal and hepatocellular carcinomas. Oncol Rep. 2010;23(3):843–51.PubMed
33.
Metadata
Title
The diagnostic potential of miR-196a-1 in colorectal cancer
Authors
Bayan Mehrjoei
Lida Haghnazari
Homayoon Bashiri
Nayebali Rezvani
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-11881-y

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