MiR-625 expression was significantly lower in endometrial cancer tissues than in matching normal samples, and circ_002577 enhanced endometrial cancer development by functioning as a sponge for miR-625, elevating IGF1R expression, and activating the PI3K/Akt pathway ( 13). By binding to the 3´-untranslated region (3´-UTR) of target ZEB2 mRNA, miR-212 restored paclitaxel sensitivity in hepatocellular carcinoma cells ( 10). MiR-212 was expressed at low levels in Paclitaxel-resistant hepatocellular carcinoma cells ( 10). Non-coding RNA molecules, such as microRNAs (miRNAs) and circular RNAs (circRNAs), have been shown to modulate gene expression and cancer cell susceptibility to paclitaxel ( 11, 12). To the best of our knowledge, there is no detailed report on the relationship between ZEB2 and paclitaxel resistance in endometrial cancer. The abrogation of ZEB2 increased paclitaxel sensitivity of lung cancer and hepatocellular carcinoma ( 9, 10). Moreover, the relationship between EZB2 overexpression and chemoresistance is increasingly established ( 7, 8). ZEB2 can trigger EMT in endometrial cancer by raising vimentin levels while decreasing E-cadherin expression ( 6). ZEB2 is important in EMT-related processes such as cancer growth, drug resistance, cancer stem cells, apoptosis, survival, cell cycle arrest, cancer recurrence, and metastasis ( 5). Furthermore, several transcription factors, including Twist1, ZEB1, ZEB2, and Snail/Slug families, are involved in the EMT process ( 4). Determining the molecular basis of endometrial cancer formation and progression will thus contribute to the development of diagnostic and therapeutic strategies to enhance survival.ĮMT is a key process that has been linked to enhanced cervical cancer invasion, metastasis, and chemoresistance and is characterized by a loss of epithelial markers such as E-cadherin and an upregulation of mesenchymal markers such as vimentin ( 4). Although the majority of endometrial cancer patients are identified with early-stage illness, which is often treatable with surgery, sometimes in conjunction with adjuvant treatment ( 2), the prognosis for metastatic and advanced illness is dismal, with a 5-year survival rate of 15 to 17% ( 3). Targeting the circ_0007534/miR-625/ZEB2 pathway might be an effective strategy for overcoming paclitaxel resistance in endometrial cancer.Įndometrial cancer is the most prevalent gynecological malignancy and the second leading cause of cancer-related mortality in women worldwide ( 1). Consequently, our data show that circ_0007534 plays a crucial role in EMT and paclitaxel resistance through miR-625/ZEB2 signaling. Our cell functional studies demonstrated that inhibiting miR-625 or increasing ZEB2 mimicked the effects of circ_0007534 overexpression. We also showed that circ_0007534 enhanced endometrial cancer aggressiveness, progression, and paclitaxel resistance by sponging microRNA-625 (miR-625) and subsequently increasing the expression of the miR-625 target gene ZEB2. Knockdown of circ_0007534 restored paclitaxel sensitivity and reversed EMT in endometrial cancer cells. Overexpression of circ_0007534 boosted endometrial cancer cell proliferation, invasion, EMT, and paclitaxel resistance. In this work, we revealed that circ_0007534 levels were significantly higher in endometrial cancer tissues, and that high circ_0007534 expression was associated with poor differentiation, advanced tumor stage, cancer invasion, cancer metastasis, and poor prognosis in endometrial cancer patients. However, whether circ_0007534 causes EMT and paclitaxel resistance in endometrial cancer is still unknown. CircRNA circ_0007534 has been described as a key oncogenic circular RNA that is upregulated in a variety of cancer tissues.
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