Endometriosis and the risk of ovarian cancer: is miR126 the Achille’s heel?

Excerpt

Endometriosis represents one of the principal causes of morbidity among premenopausal women [1]. It has been reported that endometriosis is strongly associated with an increased risk of developing ovarian cancer [1]. However, despite a higher incidence of ovarian cancer in patients affected by endometriosis, the risk factors and the underlying mechanisms linking endometriosis to ovarian cancer are not yet completely defined [1]. It has been written that microRNA126 (miR126) plays the initial role in the development and progression of endometriosis [2]. It has been found that the expression level of miR126 is considerably downregulated in ectopic endometrium in comparison with eutopic endometrium and in eutopic endometrium versus normal endometrium [2]. Intriguingly, miR126 has been shown to decrease with the progression of endometriosis [2]. Ovarian cancer represents a leading cause of gynecological cancer death worldwide [3]. microRNAs have been abnormally expressed at different levels in a number of cancers, with critical roles in the occurrence and development of malignancies [3]. miR126 has been detected to be significantly downregulated in ovarian cancer [3]. miR126 appears to act as a cancer suppressor in ovarian cancer [3]. Decreased levels of miR126 have been observed to contribute to ovarian cancer proliferation, invasion and migration [3]. Furthermore, it has been documented that lower expression level of miR126 stimulate the aggressive phenotypes and indicate poor prognosis of ovarian cancer patients [3]. On the contrary, ectopic overexpression of miR126 has been proved to inhibit ovarian cancer-cell proliferation, invasion and migration [3]. The oncogene a disintegrin and metalloproteinase 9 (ADAM9) has been found to be upregulated in ovarian cancer tissues [4]. The positive rate of ADAM9 in ovarian cancer tissue has been verified to be significantly higher than in the non-tumorous tissue [4]. What is more, increased expression level of ADAM9 has been related to high histologic grade, advanced Figo stage and greater risk of metastasis implying that ADAM9 may function as potential diagnostic and prognostic marker for the early diagnosis and treatment of ovarian cancer [4]. Interestingly, miR126 has been evidenced to influence ADAM9 [5]. It has been ascertained that ADAM9 represents a direct target gene of miR126 [5]. In detail, MiR126 has been shown to serve as a tumor-suppressor gene by reducing ADAM9 expression [5]. All these contentions led me to hypothesize that women suffering from endometriosis may be more likely to develop ovarian cancer as a result of reduced expression level of miR126 leading to aberrant expression of ADAM9. I conjecture that the combined action of miR126 downregulation and aberrant ADAM9 expression may represent a potential mechanism linking endometriosis to ovarian cancer. Thus, I speculate that miR126 may represent the Achille’s heel in susceptibility of endometriotic women to ovarian cancer and that restoration of miR126 might represent a promising tool against ovarian cancer. I hope that clinicians become aware of the possible association between endometriosis and ovarian cancer risk. …