The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract

microRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level. Let-7d is a microRNA of the conserved let-7 family that is dysregulated in female malignancies including breast cancer, ovarian cancer, endometrial cancer, and cervical cancer. Moreover, a dysregulation is observed in endometriosis and pregnancy-associated diseases such as preeclampsia and fetal growth restriction. Let-7d expression is regulated by cytokines and steroids, involving transcriptional regulation by OCT4, MYC and p53, as well as posttranscriptional regulation via LIN28 and ADAR. By downregulating a wide range of relevant mRNA targets, let-7d affects cellular processes that drive disease progression such as cell proliferation, apoptosis (resistance), angiogenesis and immune cell function. In an oncological context, let-7d has a tumor-suppressive function, although some of its functions are context-dependent. Notably, its expression is associated with improved therapeutic responses to chemotherapy in breast and ovarian cancer. Studies in mouse models have furthermore revealed important roles in uterine development and function, with implications for obstetric diseases. Apart from a possible utility as a diagnostic blood-based biomarker, pharmacological modulation of let-7d emerges as a promising therapeutic concept in a variety of female disease conditions.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:22

Enthalten in:

International journal of molecular sciences - 22(2021), 14 vom: 08. Juli

Sprache:

Englisch

Beteiligte Personen:

De Santis, Chiara [VerfasserIn]
Götte, Martin [VerfasserIn]

Links:

Volltext

Themen:

Biomarker
Biomarkers
Biomarkers, Tumor
Breast cancer
Endometriosis
Fetal growth restriction
Journal Article
Let-7
MicroRNAs
Mirnlet7 microRNA, human
Mirnlet7 microRNA, mouse
Ovarian cancer
Preeclampsia
RNA, Neoplasm
Review
Therapeutic resistance

Anmerkungen:

Date Completed 17.08.2021

Date Revised 17.08.2021

published: Electronic

Citation Status MEDLINE

doi:

10.3390/ijms22147359

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM328438456