Approximately 22.240 individuals were diagnosed with ovarian cancer in 2018 in the USA. 14.070 of the diagnosed individuals were reported to have died of ovarian cancer [40]. 2018 Globocan data showed that 7 individuals in every 100.000 were diagnosed with ovarian cancer in Turkey. The age-adjusted highest incidence ratios were generally higher than 8 in 100.000 in developed regions including the North America, Central, and East Europe. The ratios were reported as 5.8 in 100.000 in South America, and as ≤ 3 in 100.000 in Asia, and Africa[5, 41]. Ovarian cancer is the most common gynecologic tumors with the highest mortality rate. The epidemiologic studies showed that hormonal, and reproductive factors were effective in cancer pathogenesis [42]. Ovarian carcinoma involves genetic, and epigenetic changes causing cell transformation. Although significant data has been obtained about the ovarian cancer oncogenes in the last decade, there is no clear data about the etiology. Various studies showed that miRNAs had significant role in various diseases including cancer, and stated that may be used as molecular biologic indicator and even as molecular target for cancer treatment or these miRNAs might be used as chemotherapeutic agent. Ovarian cancer needs to be investigated as the disease etiology is not clearly known, and there is no available biologic indicators for the use in the early diagnosis, and treatment of the disease. Therefore, it is important to search, and investigate for new biologic indciators to be described for this disease.
Many miRNA molecules associated with the development, diagnosis, and treatment of ovarian cancer have been investigated so far. The expression levels of miR-193b, miR-532, and miR-3064 were reported to be associated with the FIGO staging used in ovarian cancer staging, tumor diameter, histologic grade, ascitis accumulation, lymph node metastasis, and with the poor prognosis [43] [44]. However, miR-506 was shown to be associated with early FIGO Staging, and good prognosis and long time survival [45]. miR-199 was reported to have lower expression in ovarian cancer, and this miRNA inhibited the related gene pathway by blocking the activation of the c-MET, HIF1-alpha HIF2-beta, and IKK-beta proteins, and thus might be a therapeutic target [46–48]. miR-152 was shown to suppress the proliferation, and metastatis abilities of ovarian cancer cells by suppressing the ERBB3 expression in ovarian cancer cell strains. Therefore, miR-152 was reported as a possible significant molecular target in cell proliferation, invasion, and metastasis of ovarian cancer [49].
Different researchers reported various miRNAs which caused the development of resistance against ovarian cancer treatment[Jin, 2018 #570]. let-7 [50], miR-9, miR-366, miR-424 [51], and miR-622 [52] were counted among these miRNAs. miRNAs circulating in the exosomal, and peripheral blood in the diagnosis and follow up of ovarian cancer were also reported. miR-21, miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205, and miR-214 were found as exosomal in serum, and were correlated with the advanced stage ovarian cancer, and miR-106b, miR-126, miR-150, miR-17, miR-20a, and miR-92a found in plasma were shown to be possibly used in the differentiation of benign ovarian disease from malignant ovarian diseases [53]. The miR-92a, and miR-200b expression levels were detected to have differentiated in the ascitis fluid generated by ovarian cancer cells, and in the urines of patients compared with the healthy controls [54]. miR-630, and miR-205 expression differences in the invasion of the ovarian cancer cells were shown to be associated with the invasive behavior of the ovarian cancer patients [55]. miR-125 was found to be effective in miR-200 family, and miR-30d miRNA genes were effective in the epithelial mesenchymal transition(EMT) [56–59]. Researchers reported that miR-222-3p expression in ovarian cancer was associated with long time survival; the lower expression of miR-9, miR-595(81), and miR-15b with higher expression of WNT7a [60] were associated with shorter survival, and poor prognosis, in addition, the differences in the expression levels of miR-141[61], miR-200a, and miR-200c were reported to be associated with the progression-free survival (PFS). The PubMed screening until 2018 various above mentioned miRNAs were investigated in ovarian cancer, and were associated with ovarian cancer diagnosis, prognosis, survival, drug resistance, and metastatic characteristics.
There is no study in the literature investigating the role of miR-1260a, and miR-1260b miRNA molecules in ovarian cancer. The expression level of miR-1260a was investigated in breast, kidney, gastric cancer, malignant melanoma, hepatocellular carcinoma, colorectal carcinoma, and esophageal squamous cell carcinoma, and was detected to have been upregulated in these cancers [23–30]. In addition, miR-1260a expression level was reported to have high level expression in the serum, and FFPE tissues of prostate cancer patients compared with the BPH controls, and higher expression was also reported in prostate cell strains [31, 32, 62]. miR-1260a expression level was shown to have upregulated in prostate cancer patients compared with the BPH controls [62]. miR-1260a was reported as one of the 13 miRNAs with diagnostic biologic indicator property used in the classification of the FFPE of prostate cancer patients in Denmark population [31], [35].
The miR-1260b was also reported to have been investigated in various cancer types except ovarian cancer in the literature, and was associated with cancer, and showed abnormal expression. miR-1260b was reported to have been abnormally, and highly expressed in the dendritic cells in human peripheral blood, and therefore was suggested to be associated with immune response [34]. miR-1260b expression level was suggested to have increased in colorectal cancer tissues particularly with lymph node metastasis, and this was suggested to be associated with lymph node metastasis, and venous invasion, and showed the early stage metastasis. miR-1260b was suggested to be an important molecular biologic indicator in CRC prognosis [63]. In addition, miR-1260b was investigated in malignant melanoma patients, and miR-1260a was reported to show a different expression pattern in the surgical resection follow up of melanoma [64]. mi1260a expression was shown to have higher expression in atypical Spitz lesions compared with the levels in benign Spitz tumors [65]. mi1260b was detected to decrease the cell migration, and invasion in nonsmall cell lung cancer cell strains (A549). This results suggest that miR-1260b had an important role in inhibiting the metastasis in NSCLC patients, and might be a target molecule in NSCLC treatment [66].
Researchers showed that miR-1260b had extremely higher expression in renal cell cancer cells compared with the levels in normal kidney cells, and this expression was correlated with cell proliferation, invasion, and shorter survival, and miR-1260 showed this effect by inhibiting the Wnt signal pathway in these incidents [67].
The comparison of the ovarian cancer patients, and healthy control group with the analysis results in the present study showed that there was a highly significant difference (p:0.000). miR-1260a, and miR-1260b expressions were found to have increased between 16.1-45.08 fold in ovarian cancer patients compared with the healthy controls. The String analysis showed that miR-1260a was mostly associated with the ribosomal protein family effective in translation. There are some studies in the literature investigating the effects of this protein family of the development of ovarian cancer [37, 38]. The results of this studies showed that the ribosomal proteins had significant and critical functions in the development of ovarian cancer, and therefore was emphasized to provide information on the pathophysiology, and treatment of ovarian dysfunctions. The evaluation of all these data showed that the deteriorations developing in the ribosomal proteins of ovarian cancer might also be indirectly generated.
String Analysis performed for miR1260b showed that miR-1260b had a close association with ‘Serin/Treonin-protein kinase family member of CHEK2 protein, and cycline dependent kinase family members of CDK4 protein. One of which is effective in DNA repair, and the other is effective in cell proliferation, and apoptosis control suggesting that these genes contributed to tumor development by inhibiting the cell proliferation, and apoptosis in ovarian cancer development [8]. All these results may conclude that the interaction of 2 different gene families with miR1260 may cause the development of ovarian cancer. These results should be investigated in future studies.
In summary, the significant expression of miR1260, and miR1260b in the peripheral blood lymphocytes of ovarian cancer patients compared with the healthy controls was first demonstrated by our group, the gene interactions of these two genes are suggested to have diagnostic significance owing to causing ovarian cancer. In addition, the present study suggests that miR1260a, and miR1260b molecules which were detected to have differentiated particularly in peripheral blood had prognostic significance, and therefore might be used as bioindicators. These molecules must also be investigated in the benign ovarian diseases for better understanding their importance in the early diagnosis, and diagnostic importance in ovarian cancer. In addition, the comparative investigation of the levels of these molecules in the peripheral blood during treatment is required to be studied for identifying their safety as prognostic biologic indicator.