The Gynecologic Oncology Institute investigative team came upon this additional novel marker therapy strategy.
Ovarian cancer is a significant cause of death from gynecologic cancer. There are about 14,000 cases died of ovarian cancer each year in the United States. Overall survival of women with advanced ovarian cancer was rarely improved in recent years. Recurrence and chemotherapy resistance are the two most common causes of high mortality for ovarian cancer patients. The acquisition of cisplatin resistance usually occurs in about 25% of patients within six months of chemotherapy. The standard therapy for ovarian cancer is surgery combined with cisplatin chemotherapy at present.
In recent years, the roles of lncRNAs in various cancers were discussed in many reports. Emerging evidence revealed that lncRNA ANRIL was elevated in tumor tissues, and it served as oncogene roles in numerous malignancies.1–4 Besides, ANRIL regulated cancer cell proliferation, invasion, migration and apoptosis.3–5 Furthermore, the study has reported that ANRIL was upregulated in ovarian cancer.6 Qiu et al revealed that ANRIL regulated ovarian cancers carcinogenesis and might have diagnostic value in ovarian cancer.3 In addition, the resistance of ovarian cancer cells to cisplatin was affected by ANRIL.7 Additionally, ANRIL facilitated ovarian cancer cell proliferation and cell cycle progression.5 It is well documented that ANRIL interacted with miRNAs to modulate cancer progression, such as miR-186,6 miR-99a/miR-449a,8 miR-125a,9 miR-323.10 Thus, we speculated that ANRIL might regulate ovarian cancer progression via sponging miRNAs.
A study confirmed that ANRIL was upregulated while miR-324-5p was down-regulated in laryngeal squamous cell cancer.11 Of note, the effect of the ANRIL/miR-324-5p axis on ovarian cancer was unclear, which might be similar to that in laryngeal squamous cell cancer. According to the TargetScan prediction of RNA action sites, Ran was considered as a target of miR-324-5p. Interestingly, the highly expressed Ran also accelerated the development of ovarian cancer.12,13 However, the association between miR-324-5p and Ran was undefined. Hence, we aimed to investigate the role of the ANRIL/miR-324-5p/Ran axis in ovarian cancer progression. The malignant behaviors such as migration, invasion, cancer stem characteristics, and cell tumorigenicity were discussed in this study.
This study identified the regulatory mechanism of ANRIL/miR-324-5p/Ran axis on the malignant progression of ovarian cancer, making ANRIL a meaningful target for ovarian cancer therapy.
Taken together, the downregulation of ANRIL suppressed the cell proliferation, metastasis, drug resistance, and stem-like properties of ovarian cancer cells. In conclusion, this study supplemented the tumorigenic role of ANRIL in ovarian cancer. Excitingly, we revealed a new regulatory mechanism of ANRIL in ovarian cancer malignant behaviors, including excessive proliferation, invasion, metastasis, EMT, and chemotherapy resistance. LncRNA ANRIL involves the progression of ovarian cancer through miR-324-5p/Ran axis, making the axis meaning targets for ovarian cancer therapy.
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