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Published on: August 2, 2024
Circular RNA circTNPO3 Regulates Paclitaxel Resistance of Ovarian Cancer Cells by miR-1299/NEK2 Signaling Pathway
Bing Xia1, Zitong Zhao1, Yinnayuan Wu1
1Department of Gynecologic Oncology, Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiang-Ya School of Medicine, Central South University, Changsha 410078, China.
Abstract:
Circular RNAs (circRNAs) were recently reported to be involved in the pathogenesis of ovarian cancer (OC); however, the molecular mechanisms of circRNAs in tumor progression and paclitaxel (PTX) resistance of OC remain largely undetermined. Here, we focused on circTNPO3 (hsa_circ_0001741), which is located on chromosome 7 (chr7): 128655032-128658211 and derived from TNPO3 gene, and thus we termed as circTNPO3. By microarray and qRT-PCR we identified circTNPO3 to be dramatically high expressed in OC samples and correlated with PTX resistance. Functionally, knockdown of circTNPO3 enhanced cell sensitivity to PTX via promoting PTX-induced apoptosis in vitro and in vivo. In mechanism, circTNPO3 acted as a sponge for microRNA-1299 (miR-1299), and NEK2 (NIMA-related kinase 2) was revealed to be target gene of miR-1299. Subsequently, functional assays illustrated that the oncogenic effects of circTNPO3 were attributed to the regulation of miR-1299/NEK2 axis. In conclusion, circTNPO3 contributed to PTX resistance of OC cells at least partly through upregulating NEK2 expression by sponging miR-1299. circTNPO3/miR-1299/NEK2 signaling pathway might play vital roles in the tumorigenesis and chemoresistance of OC.
Insights
Circular RNAs (circRNAs) like circTNPO3 are highly expressed in ovarian cancer (OC), promoting paclitaxel (PTX) resistance. Targeting the circTNPO3/miR-1299/NEK2 pathway can re-sensitize OC cells to PTX therapy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in ovarian cancer (OC) pathogenesis.
- The specific roles and mechanisms of circRNAs in OC progression and paclitaxel (PTX) resistance are not fully understood.
Purpose of the Study:
- To investigate the role of circTNPO3 in OC development and PTX resistance.
- To elucidate the molecular mechanism underlying circTNPO3's function in OC.
Main Methods:
- Microarray and qRT-PCR to assess circTNPO3 expression in OC tissues.
- In vitro and in vivo experiments to evaluate the effect of circTNPO3 knockdown on PTX sensitivity and apoptosis.
- Mechanism studies involving microRNA sponging and target gene validation.
Main Results:
- circTNPO3 expression is significantly upregulated in OC tissues and correlates with PTX resistance.
- Knockdown of circTNPO3 enhances OC cell sensitivity to PTX by promoting apoptosis.
- circTNPO3 functions as a molecular sponge for miR-1299, leading to increased NEK2 expression.
Conclusions:
- circTNPO3 promotes PTX resistance in OC by upregulating NEK2 via the miR-1299 sponging mechanism.
- The circTNPO3/miR-1299/NEK2 signaling pathway is a potential therapeutic target for overcoming chemoresistance in OC.
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