Uterine leiomyomas, also called uterine fibroids, are benign tumors that originate from the smooth muscle of the uterus. Fibroids are the most common non-cancerous tumor of the female genital tract, affecting 80% of all women during their lifetime. More than half of women develop fibroids during their reproductive years, often complicating pregnancy. Fibroids are a major source of heavy uterine bleeding, pain, and reduced fertility, resulting in reduced quality of life and significant stress for many women.
Treatments for fibroids consist of surgery, including hysterectomy or myomectomy, hormonal modulators, such as gonadotropin-releasing hormone agonists, and uterine arterial embolization (UAE), which blocks the blood supply to the tumor. The only true cure is surgical resection, with hormonal approaches and UAE estimated to shrink tumors by 30-40%. Bleeding and pain can also be significantly reduced by these treatments. However, results vary, and many women do not derive benefit from available procedures. Progress in designing new treatments has been slow, largely because we have a poor understanding of the biology of fibroids.
A new study recently identified a molecule that is expressed at abnormally high levels in fibroids. The molecule, H19, belongs to a class of molecules called long noncoding RNAs. H19 was found at increased levels in fibroid tissues from 30 women, including 20 premenopausal, compared with normal uterine myometrium tissues from the same women. High expression of H19 caused fibroid cells to double in number faster, whereas getting rid of H19 actually slowed down growth. Importantly, H19 also drove expression of molecular profiles that have previously been linked to fibroid development and growth. Thus, H19 may function upstream as a key regulator of fibroids. Estrogen and progesterone are thought to influence fibroid growth. This new study showed that combined exposure to estrogen and progesterone increased H19 expression and other fibroid-promoting genes. When H19 was eliminated, the effects of estrogen and progesterone were abolished.
Although these results are preliminary, they are exciting for several reasons. We know so little about fibroids, and options for women who suffer from this debilitating chronic medical condition are limited. Fibroids receive little attention from the research community. The few studies that have been published in recent years are mostly preclinical in animal models and do not generally include patient samples. This new study used matched human fibroid and normal myometrium tissue from the same patients. This study also explored molecular mechanisms and biology, demonstrating cause and effect and not purely correlative findings.
Further studies are urgently needed to confirm the role of H19 and to identify other major mechanisms promoting fibroids. Identification of key regulators of fibroid development and growth moves us one step closer to understanding this disease and improving therapeutic options for women.
Reference: Cao T et al. Oncogene 2019 May 15