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
SN - 0143-3334
VL - 35
SP - 76
EP - 85
JO - Carcinogenesis
JF - Carcinogenesis
IS - 1
ER -
