Effects of Lactobacillus acidophilus and Bifidobacterium bifidum Probiotics on the Expression of MicroRNAs 135b, 26b, 18a and 155, and Their Involving Genes in Mice Colon Cancer
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A wide range of sources supports that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora. In this case, it seems that the probiotics may have a possible molecular mechanism via microRNAs (miRNAs). The present study is aimed to evaluate the effects of Lactobacillus acidophilus and Bifidobacterium bifidum probiotics on the expression of miRNAs 135b, 26b, 18a, and 155 and their target genes, including APC, PTEN, KRAS, and PU.1 in mouse azoxymethane (AOM)-induced colon cancer. Thirty-eight male BALB/c mice were randomly divided into four groups: the control, AOM, Lactobacillus acidophilus, and Bifidobacterium bifidum to deliberate the effects of the probiotics on the miRNAs and their target genes. Except for the control group, the rest groups were weekly given AOM (15 mg/kg, s.c) in three consecutive weeks to induce mouse colon cancer. The animals were given 1.5 g powders of L. acidophilus (1 × 109 cfu/g) and B. bifidum (1 × 109 cfu/g) in 30 cc drinking water in the related groups for 5 months. At the end of the study, the animals were sacrificed and their blood and colon samples were removed for the molecular analyses. The results showed that the expression of the miR-135b, miR-155, and KRAS was increased in the AOM group compared to the control group in both the plasma and the colon tissue samples, and the consumption of the probiotics decreased their expression. Moreover, the miR-26b, miR-18a, APC, PU.1, and PTEN expressions were decreased in the AOM group compared to the control group and the consumption of the probiotics increased their expressions. It seems that Lactobacillus acidophilus and Bifidobacterium bifidum though increasing the expression of the tumor suppressor miRNAs and their target genes and decreasing the oncogenes can improve colon cancer treatment.
KeywordsColon cancer Gene MiRNA Lactobacillus acidophilus Bifidobacterium bifidum
This study was supported by Iran University of Medical Sciences (Grant No. 24067).
Compliance with Ethical Standards
All procedures performed in studies involving animals were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Conflict of Interest
The authors of the manuscript have no conflicts of interest to declare and are responsible for the content of the paper.
None of the funding sources had any role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
- 4.Hotel ACP (2001) Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Cordoba, ArgentinaGoogle Scholar
- 10.Agah S, Alizadeh AM (2018) More protection of Lactobacillus acidophilus than Bifidobacterium bifidum probiotics on azoxymethane-induced mouse colon cancer. Probiotics Antimicrob Proteins. https://doi.org/10.1007/s12602-018-9425-8
- 11.Khavari-Daneshvar H, Mosavi M, Khodayari H, Rahimi E, Ranji P, Mohseni AH, Mahmudian R, Shidfar F, Agah S, Alizadeh AM (2017) Modifications of mice gut microflora following oral consumption of Lactobacillus acidophilus and Bifidobacterium bifidum probiotics. Turk J Med Sci 47(2):689–694CrossRefGoogle Scholar
- 20.Endzelins E, Berger A, Melne V, Bajo-Santos C, Sobolevska K, Abols A, Rodriguez M, Santare D, Rudnickiha A, Lietuvietis V (2017) Detection of circulating miRNAs: comparative analysis of extracellular vesicle-incorporated miRNAs and cell-free miRNAs in whole plasma of prostate cancer patients. BMC Cancer 17(1):730. https://doi.org/10.1186/s12943-016-0523-5 CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Khori V, Shalamzari SA, Isanejad A, Alizadeh AM, Alizadeh S, Khodayari S, Khodayari H, Shahbazi S, Zahedi A, Sohanaki H (2015) Effects of exercise training together with tamoxifen in reducing mammary tumor burden in mice: possible underlying pathway of miR-21. Eur J Pharmacol 765:179–187CrossRefGoogle Scholar
- 25.Sharbati-Tehrani S, Kutz-Lohroff B, Bergbauer R, Scholven J, Einspanier R (2008) miR-Q: a novel quantitative RT-PCR approach for the expression profiling of small RNA molecules such as miRNAs in a complex sample. BMC Mol Biol 9:34. https://doi.org/10.1186/1471-2199-9-34 CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Bandres E, Cubedo E, Agirre X, Malumbres R, Zarate R, Ramirez N, Abajo A, Navarro A, Moreno I, Monzo M, Garcia-Foncillas J (2006) Identification by real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer 5:29. https://doi.org/10.1186/1476-4598-5-29 CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Vigorito E Perks KL, Abreu-Goodger C, Bunting S, Xiang Z, Kohlhaas S, Das PP, Miska EA, Rodriguez A, Bradley A, Smith KG, Rada C, Enright AJ, Toellner KM, Maclennan IC, Turner M (2007) MicroRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity 27:847–859CrossRefGoogle Scholar
- 44.Trotman LC, Niki M, Dotan ZA, Koutcher JA, Di Cristofano A, Xiao A, Khoo AS, Roy-Burman P, Greenberg NM, Van Dyke T, Cordon-Cardo C, Pandolfi PP (2003) PTEN dose dictates cancer progression in the prostate. PLoS Biol 1(3):E59. https://doi.org/10.1371/journal.pbio.0000059 CrossRefPubMedPubMedCentralGoogle Scholar
- 49.Hiraki M, Nishimura J, Takahashi H, Wu X, Takahashi Y, Miyo M, Nishida N, Uemura M, Hata T, Takemasa I, Mizushima T, Soh JW, Doki Y, Mori M, Yamamoto H (2015) Concurrent targeting of KRAS and AKT by miR-4689 is a novel treatment against mutant KRAS colorectal cancer. Mol Ther Nucleic Acids 4:e231. https://doi.org/10.1038/mtna.2015.5 CrossRefPubMedPubMedCentralGoogle Scholar
- 50.Gill RK, Dudeja PK (2011) A novel facet to consider for the effects of butyrate on its target cells. Focus on “the short-chain fatty acid butyrate is a substrate of breast cancer resistance protein”. Am J Physiol Cell Physiol 301(5):C977–C979. https://doi.org/10.1152/ajpcell.00290.2011 CrossRefPubMedPubMedCentralGoogle Scholar