Deregulation of cancer-related miRNAs is a common event in both benign and malignant human breast tumors

Andliena Tahiri, Suvi-Katri Leivonen, Torben Lüders, Israel Steinfeld, Miriam Ragle Aure, Jürgen Geisler, Rami Mäkelä, Silje Nord, Margit L.H. Riis, Zohar Yakhini, Kristine Kleivi Sahlberg, Anne-Lise Børressen-Dale, Merja Perälä, Ida R.K. Bukholm, Vessela N. Kristensen (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

74 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) are endogenous non-coding RNAs, which play an essential role in the regulation of gene expression during carcinogenesis. The role of miRNAs in breast cancer has been thoroughly investigated, and although many miRNAs are identified as cancer related, little is known about their involvement in benign tumors. In this study, we investigated miRNA expression profiles in the two most common types of human benign tumors (fibroadenom a/fibroadenomatosis) and in malignant breast tumors and explored their role as oncomirs and tumor suppressor miRNAs. Here, we identified 33 miRNAs with similar deregulated expression in both benign and malignant tumors compared with the expression levels of those in normal tissue, including breast cancer-related miRNAs such as let-7, miR-21 and miR-155. Additionally, messenger RNA (mRNA) expression profiles were obtained for some of the same samples. Using integrated mRNA/miRNA expression analysis, we observed that overexpression of certain miRNAs co-occurred with a significant downregulation of their candidate target mRNAs in both benign and malignant tumors. In support of these findings, in vitro functional screening of the downregulated miRNAs in nonmalignant and breast cancer cell lines identified several possible tumor suppressor miRNAs, including miR-193b, miR-193a-3p, miR-126, miR-134, miR-132, miR-486-5p, miR-886-3p, miR-195 and miR-497, showing reduced growth when re-expressed in cancer cells. The finding of deregulated expression of oncomirs and tumor suppressor miRNAs in benign breast tumors is intriguing, indicating that they may play a role in proliferation. A role of cancer-related miRNAs in the early phases of carcinogenesis and malignant transformation can, therefore, not be ruled out
Original languageEnglish
Pages (from-to)76-85
JournalCarcinogenesis
Volume35
Issue number1
DOIs
Publication statusPublished - 2014
MoE publication typeA1 Journal article-refereed

Fingerprint

MicroRNAs
Breast Neoplasms
Neoplasms
Messenger RNA
Carcinogenesis
Down-Regulation
Untranslated RNA
Gene Expression Regulation

Cite this

Tahiri, A., Leivonen, S-K., Lüders, T., Steinfeld, I., Aure, M. R., Geisler, J., ... Kristensen, V. N. (2014). Deregulation of cancer-related miRNAs is a common event in both benign and malignant human breast tumors. Carcinogenesis, 35(1), 76-85. https://doi.org/10.1093/carcin/bgt333
Tahiri, Andliena ; Leivonen, Suvi-Katri ; Lüders, Torben ; Steinfeld, Israel ; Aure, Miriam Ragle ; Geisler, Jürgen ; Mäkelä, Rami ; Nord, Silje ; Riis, Margit L.H. ; Yakhini, Zohar ; Sahlberg, Kristine Kleivi ; Børressen-Dale, Anne-Lise ; Perälä, Merja ; Bukholm, Ida R.K. ; Kristensen, Vessela N. / Deregulation of cancer-related miRNAs is a common event in both benign and malignant human breast tumors. In: Carcinogenesis. 2014 ; Vol. 35, No. 1. pp. 76-85.
@article{da40d6f8a7ff4b2ab546904aa9cf11fb,
title = "Deregulation of cancer-related miRNAs is a common event in both benign and malignant human breast tumors",
abstract = "MicroRNAs (miRNAs) are endogenous non-coding RNAs, which play an essential role in the regulation of gene expression during carcinogenesis. The role of miRNAs in breast cancer has been thoroughly investigated, and although many miRNAs are identified as cancer related, little is known about their involvement in benign tumors. In this study, we investigated miRNA expression profiles in the two most common types of human benign tumors (fibroadenom a/fibroadenomatosis) and in malignant breast tumors and explored their role as oncomirs and tumor suppressor miRNAs. Here, we identified 33 miRNAs with similar deregulated expression in both benign and malignant tumors compared with the expression levels of those in normal tissue, including breast cancer-related miRNAs such as let-7, miR-21 and miR-155. Additionally, messenger RNA (mRNA) expression profiles were obtained for some of the same samples. Using integrated mRNA/miRNA expression analysis, we observed that overexpression of certain miRNAs co-occurred with a significant downregulation of their candidate target mRNAs in both benign and malignant tumors. In support of these findings, in vitro functional screening of the downregulated miRNAs in nonmalignant and breast cancer cell lines identified several possible tumor suppressor miRNAs, including miR-193b, miR-193a-3p, miR-126, miR-134, miR-132, miR-486-5p, miR-886-3p, miR-195 and miR-497, showing reduced growth when re-expressed in cancer cells. The finding of deregulated expression of oncomirs and tumor suppressor miRNAs in benign breast tumors is intriguing, indicating that they may play a role in proliferation. A role of cancer-related miRNAs in the early phases of carcinogenesis and malignant transformation can, therefore, not be ruled out",
author = "Andliena Tahiri and Suvi-Katri Leivonen and Torben L{\"u}ders and Israel Steinfeld and Aure, {Miriam Ragle} and J{\"u}rgen Geisler and Rami M{\"a}kel{\"a} and Silje Nord and Riis, {Margit L.H.} and Zohar Yakhini and Sahlberg, {Kristine Kleivi} and Anne-Lise B{\o}rressen-Dale and Merja Per{\"a}l{\"a} and Bukholm, {Ida R.K.} and Kristensen, {Vessela N.}",
year = "2014",
doi = "10.1093/carcin/bgt333",
language = "English",
volume = "35",
pages = "76--85",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "1",

}

Tahiri, A, Leivonen, S-K, Lüders, T, Steinfeld, I, Aure, MR, Geisler, J, Mäkelä, R, Nord, S, Riis, MLH, Yakhini, Z, Sahlberg, KK, Børressen-Dale, A-L, Perälä, M, Bukholm, IRK & Kristensen, VN 2014, 'Deregulation of cancer-related miRNAs is a common event in both benign and malignant human breast tumors', Carcinogenesis, vol. 35, no. 1, pp. 76-85. https://doi.org/10.1093/carcin/bgt333

Deregulation of cancer-related miRNAs is a common event in both benign and malignant human breast tumors. / Tahiri, Andliena; Leivonen, Suvi-Katri; Lüders, Torben; Steinfeld, Israel; Aure, Miriam Ragle; Geisler, Jürgen; Mäkelä, Rami; Nord, Silje; Riis, Margit L.H.; Yakhini, Zohar; Sahlberg, Kristine Kleivi; Børressen-Dale, Anne-Lise; Perälä, Merja; Bukholm, Ida R.K.; Kristensen, Vessela N. (Corresponding Author).

In: Carcinogenesis, Vol. 35, No. 1, 2014, p. 76-85.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Deregulation of cancer-related miRNAs is a common event in both benign and malignant human breast tumors

AU - Tahiri, Andliena

AU - Leivonen, Suvi-Katri

AU - Lüders, Torben

AU - Steinfeld, Israel

AU - Aure, Miriam Ragle

AU - Geisler, Jürgen

AU - Mäkelä, Rami

AU - Nord, Silje

AU - Riis, Margit L.H.

AU - Yakhini, Zohar

AU - Sahlberg, Kristine Kleivi

AU - Børressen-Dale, Anne-Lise

AU - Perälä, Merja

AU - Bukholm, Ida R.K.

AU - Kristensen, Vessela N.

PY - 2014

Y1 - 2014

N2 - MicroRNAs (miRNAs) are endogenous non-coding RNAs, which play an essential role in the regulation of gene expression during carcinogenesis. The role of miRNAs in breast cancer has been thoroughly investigated, and although many miRNAs are identified as cancer related, little is known about their involvement in benign tumors. In this study, we investigated miRNA expression profiles in the two most common types of human benign tumors (fibroadenom a/fibroadenomatosis) and in malignant breast tumors and explored their role as oncomirs and tumor suppressor miRNAs. Here, we identified 33 miRNAs with similar deregulated expression in both benign and malignant tumors compared with the expression levels of those in normal tissue, including breast cancer-related miRNAs such as let-7, miR-21 and miR-155. Additionally, messenger RNA (mRNA) expression profiles were obtained for some of the same samples. Using integrated mRNA/miRNA expression analysis, we observed that overexpression of certain miRNAs co-occurred with a significant downregulation of their candidate target mRNAs in both benign and malignant tumors. In support of these findings, in vitro functional screening of the downregulated miRNAs in nonmalignant and breast cancer cell lines identified several possible tumor suppressor miRNAs, including miR-193b, miR-193a-3p, miR-126, miR-134, miR-132, miR-486-5p, miR-886-3p, miR-195 and miR-497, showing reduced growth when re-expressed in cancer cells. The finding of deregulated expression of oncomirs and tumor suppressor miRNAs in benign breast tumors is intriguing, indicating that they may play a role in proliferation. A role of cancer-related miRNAs in the early phases of carcinogenesis and malignant transformation can, therefore, not be ruled out

AB - MicroRNAs (miRNAs) are endogenous non-coding RNAs, which play an essential role in the regulation of gene expression during carcinogenesis. The role of miRNAs in breast cancer has been thoroughly investigated, and although many miRNAs are identified as cancer related, little is known about their involvement in benign tumors. In this study, we investigated miRNA expression profiles in the two most common types of human benign tumors (fibroadenom a/fibroadenomatosis) and in malignant breast tumors and explored their role as oncomirs and tumor suppressor miRNAs. Here, we identified 33 miRNAs with similar deregulated expression in both benign and malignant tumors compared with the expression levels of those in normal tissue, including breast cancer-related miRNAs such as let-7, miR-21 and miR-155. Additionally, messenger RNA (mRNA) expression profiles were obtained for some of the same samples. Using integrated mRNA/miRNA expression analysis, we observed that overexpression of certain miRNAs co-occurred with a significant downregulation of their candidate target mRNAs in both benign and malignant tumors. In support of these findings, in vitro functional screening of the downregulated miRNAs in nonmalignant and breast cancer cell lines identified several possible tumor suppressor miRNAs, including miR-193b, miR-193a-3p, miR-126, miR-134, miR-132, miR-486-5p, miR-886-3p, miR-195 and miR-497, showing reduced growth when re-expressed in cancer cells. The finding of deregulated expression of oncomirs and tumor suppressor miRNAs in benign breast tumors is intriguing, indicating that they may play a role in proliferation. A role of cancer-related miRNAs in the early phases of carcinogenesis and malignant transformation can, therefore, not be ruled out

U2 - 10.1093/carcin/bgt333

DO - 10.1093/carcin/bgt333

M3 - Article

VL - 35

SP - 76

EP - 85

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 1

ER -