miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR

Lukosevicius, Rokas; Juzenas, Simonas; Salteniene, Violeta; Kulokiene, Ugne; Arstikyte, Justina; Hemmrich-Stanisak, Georg; Franke, Andre; Link, Alexander; Ruzgys, Paulius; Satkauskas, Saulius; Pauzas, Henrikas; Latkauskas, Tadas; Kiudelis, Gediminas; Balaguer, Francesc; Kupcinskas, Juozas; Skieceviciene, Jurgita

doi:10.3390/ijms23042107

Open AccessArticle

miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR

by

Rokas Lukosevicius

^1,†

,

Simonas Juzenas

^1,2,†

,

Violeta Salteniene

¹

,

Ugne Kulokiene

¹,

Justina Arstikyte

¹,

Georg Hemmrich-Stanisak

²

,

Andre Franke

²,

Alexander Link

³

,

Paulius Ruzgys

⁴

,

Saulius Satkauskas

⁴

,

Henrikas Pauzas

⁵,

Tadas Latkauskas

⁵,

Gediminas Kiudelis

⁶,

Francesc Balaguer

⁷

,

Juozas Kupcinskas

^1,6,*,‡

and

Jurgita Skieceviciene

^1,*,‡

¹

Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania

²

Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany

³

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, 39106 Magdeburg, Germany

⁴

Biophysical Research Group, Faculty of Natural Sciences, Vytautas Magnus University, 44248 Kaunas, Lithuania

⁵

Department of Surgery, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania

⁶

Department of Gastroenterology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania

⁷

Department of Gastroenterology, Hospital Clínic Barcelona, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), University of Barcelona, 08036 Barcelona, Spain

^*

Authors to whom correspondence should be addressed.

^†

These authors equally contributed to this work.

^‡

These authors jointly supervised this work.

Int. J. Mol. Sci. 2022, 23(4), 2107; https://doi.org/10.3390/ijms23042107

Submission received: 28 December 2021 / Revised: 26 January 2022 / Accepted: 10 February 2022 / Published: 14 February 2022

(This article belongs to the Section Biochemistry)

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Abstract

Regulatory changes occurring early in colorectal cancer development remain poorly investigated. Since the majority of cases develop from polyps in the adenoma-carcinoma transition, a search of early molecular features, such as aberrations in miRNA expression occurring prior to cancer development, would enable identification of potentially causal, rather than consequential, candidates in the progression of polyp to cancer. In the current study, by employing small RNA-seq profiling of colon biopsy samples, we described differentially expressed miRNAs and their isoforms in the adenoma-carcinoma transition. Analysis of healthy-adenoma-carcinoma sequence in an independent validation group enabled us to identify early deregulated miRNAs including hsa-miR-1246 and hsa-miR-215-5p, the expressions of which are, respectively, gradually increasing and decreasing. Loss-of-function experiments revealed that inhibition of hsa-miR-1246 lead to reduced cell viability, colony formation, and migration rate, thereby indicating an oncogenic effect of this miRNA in vitro. Subsequent western blot and luciferase reporter assay provided evidence of hsa-miR-1246 being involved in the regulation of target AXIN2 and CFTR genes’ expression. To conclude, the present study revealed possible involvement of hsa-miR-1246 in early colorectal cancer development and regulation of tumor suppressors AXIN2 and CFTR.

Keywords: colorectal cancer; adenomatous polyps; microRNA; isomiR; small RNA-seq

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MDPI and ACS Style

Lukosevicius, R.; Juzenas, S.; Salteniene, V.; Kulokiene, U.; Arstikyte, J.; Hemmrich-Stanisak, G.; Franke, A.; Link, A.; Ruzgys, P.; Satkauskas, S.; et al. miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR. Int. J. Mol. Sci. 2022, 23, 2107. https://doi.org/10.3390/ijms23042107

AMA Style

Lukosevicius R, Juzenas S, Salteniene V, Kulokiene U, Arstikyte J, Hemmrich-Stanisak G, Franke A, Link A, Ruzgys P, Satkauskas S, et al. miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR. International Journal of Molecular Sciences. 2022; 23(4):2107. https://doi.org/10.3390/ijms23042107

Chicago/Turabian Style

Lukosevicius, Rokas, Simonas Juzenas, Violeta Salteniene, Ugne Kulokiene, Justina Arstikyte, Georg Hemmrich-Stanisak, Andre Franke, Alexander Link, Paulius Ruzgys, Saulius Satkauskas, and et al. 2022. "miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR" International Journal of Molecular Sciences 23, no. 4: 2107. https://doi.org/10.3390/ijms23042107

APA Style

Lukosevicius, R., Juzenas, S., Salteniene, V., Kulokiene, U., Arstikyte, J., Hemmrich-Stanisak, G., Franke, A., Link, A., Ruzgys, P., Satkauskas, S., Pauzas, H., Latkauskas, T., Kiudelis, G., Balaguer, F., Kupcinskas, J., & Skieceviciene, J. (2022). miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR. International Journal of Molecular Sciences, 23(4), 2107. https://doi.org/10.3390/ijms23042107

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miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR

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