Background: Uterine leiomyoma, also called fibroid, is a benign tumor that arises due to monoclonal transformation of myometrium, the smooth muscle cell layer of the uterus. Fibroids cause several complications including infertility, miscarriage, bleeding, pain, and dysmenorrhea. Recent studies have revealed the role of mutations in MED12 gene exon 2 in various populations; however, the reported frequency of these mutations differs between reports. In addition, it is suggested that mutations in exon 1 may also play a role in leiomyoma. The aim of the present study was to screen for MED12 exon 1 mutations in leiomyoma tissue samples of Iranian patients. . Methods: We performed mutational analysis of exon 1 and the flanking intronic regions using multitemperature single-strand conformational polymorphism (MSSCP) and sequencing analyses in 120 uterine leiomyoma samples. Results: No mutations were detected in exon 1 of MED12 in our samples. Conclusions: According to the literature and the present results, mutations in the MED12 exon 1 are rare. However, we could not ignore the role of these mutations in developing leiomyoma.

Prostate cancer is a disease that depends on androgenic stimulation and is thus commonly treated with androgen deprivation therapy (ADT). ADT is highly successful initially; however, patients inevitably relapse at which point the cancer grows independently of androgens and is termed castration-resistant prostate cancer (CRPC). CRPC develops through various mechanisms, one of these being crosstalk of the androgen receptor (AR) signaling pathway with other signaling pathways. Congruently, prior work has shown that androgen deprivation induces SHH signaling, which subsequently promotes activation of AR-dependent gene expression to promote cell growth. Mechanistically, this crosstalk involves a physical interaction between AR and components of SHH signaling, specifically proteins of the GLI transcription factor family. These findings thus suggest that activation of SHH signaling could promote the recurrence of cell growth in the absence of androgens to ultimately lead to progression towards CRPC. In this study, we have investigated this mechanism in a subset of prostate cancer that harbors genetic alterations within the Mediator subunit 12 (MED12). We found that loss of MED12 promotes the expression of GLI3 target genes which subsequently drives excessive cell growth in the absence of androgens. Thus, we conclude that genetic alterations within MED12 promote CRPC through hyperactivated GLI3 dependent sonic hedgehog signaling.

Breast cancer remains to be the second leading cause of cancer deaths worldwide thereby highlighting the critical need to find superior treatment strategies for this disease. In the current era of cancer treatment, personalized medicine is garnering much attention as this type of treatment is more selective thereby minimizing harmful side effects. Personalized medicine is dependent upon knowing the underlying genetic landscape of the initial tumor. In our study, we focused our efforts on a specific subset of breast cancer that harbors genetic alterations in the Mediator subunit 12 (MED12). Our results show that loss of MED12 leads to enhanced cellular proliferation and colony formation of breast cancer cells through a mechanism that involves activation of GLI3-dependent SHH signaling, a pathway that is central to breast development and homeostasis. To find a personalized treatment option for this subset of breast cancer, we employed a natural compound screening strategy which uncovered a total of ten compounds that selectively target MED12 knockdown breast cancer cells. Our results show that two of these ten compounds, solasonine and alisol B23-acetate, block GLI3-dependent SHH signaling which leads to a reversal of enhanced cellular proliferation and colony formation ability. Thus, our findings provide promising insight into a novel personalized treatment strategy for patients suffering from MED12-altered breast cancer.

Introduction: Lujan-Fryns syndrome (LFS) is an X-linked disorder characterized by varying degrees of symptoms, including mental retardation, Marfanoid habitus, facial deformities, hyper nasal speech, and psychopathology and related behavioral abnormalities. The prevalence and full spectrum of LFS’ s clinical symptoms remain unknown, but the disease is reportedly caused by at least one mutation in the mediator complex subunit 12 (MED12) gene. Case Presentation: This study reports the case of an 18-year-old male with moderate mental disability, a height exceeding the 97th percentile, marfanoid characteristics, obvious craniofacial appearance, and psychiatric and behavioral disorders. Adults with LFS are usually tall, but their heights still fall within the normal range. Conclusions: The higher-than-normal mean height of the young man and psychosis led us to conclude that patients with LFS may be those taller than the normal range. The results provided insights into clinical and therapeutic remedies and highlighted the need to carefully examine the psychological and neuropsychological symptoms of LFS.

More than 75% of women have uterine fibroids (leiomyomas), which may have major morbid effects. By far, they are the main reason for a hysterectomy. Smooth muscle cells and fibroblasts make up the complicated cellular assemblage known as fibroids. They generally develop from somatic mutations, most often MED12, and are rich in the extracellular matrix. They provide chances to investigate fundamental mechanisms due to their lack of inhibition of growth and their capacity to display aspects of malignancy while remaining histologically and physiologically benign. The processes behind the genesis and evolution of leiomyomas remain a mystery. In the current research, 102 individuals were found, 12 of whom were removed for a variety of reasons, and 90 patients' data were analyzed. Age prevalence is evaluated in the topic, and risk factors, pharmaceutical therapy, surgical alternatives, and consequences are examined. According to this research, women between the ages of 31 and 40 are more likely to develop uterine fibroids, and age, obesity, and hormone imbalance are risk factors. Anti-fibrinolytic agents are a first-line therapy in the pharmacological management of menstrual bleeding. Hysterectomy is the recommended surgical procedure for the treatment of uterine fibroids. Our research found that excessive or prolonged bleeding and unfavourable pregnancy outcomes were the main symptoms. This research shows that uterine fibroids have a major influence on one's quality of life.