GATA1-induced upregulation of LINC01503 promotes carboplatin resistance in ovarian carcinoma by upregulating PD-L1 via sponging miR-766-5p

Abstract

Background Ovarian Carcinoma (OCa) is a high-mortality malignancy derived from female reproductive system. Increasing evidence has identified long non-coding RNAs (lncRNAs) as important regulators in OCa chemoresistance. In this study, we intended to explore the role of LINC01503 in OCa resistance to carboplatin (CBP). Methods Gene expression was measured by reverse transcription-quantitative PCR (RT-qPCR) in OCa cells. Western blot was adopted to detect protein levels of GATA1, PD-L1, E-cadherin, N-cadherin, Vimentin, Bcl-2, Bax, cleaved caspase-3. To assess the effects of LINC01503 on the resistance of OCa cells to CBP, Cell Counting Kit-8 (CCK-8), colony formation, Transwell, and flow cytometry experiments were performed to evaluate half-maximal inhibitory concentration (IC50), cell viability, migrative and invasive ability, as well as cell apoptosis. Dual-luciferase reporter assay was employed to assess the associations between the genes. Results LINC01503 was upregulated in CBP-resistant OCa cells. LINC01503 knockdown reduced CBP resistance in OCa cells. Besides, GATA-binding protein 1 (GATA1) activated LINC01503 transcription in CBP-resistant OCa cells. MiR-766-5p was lowly expressed in CBP-resistant cells and confirmed as a target for LINC01503. In addition, miR-766-5p overexpression increased CBP sensitivity in OCa cells. PD-L1 was verified as the target of miR-766-5p. Besides, LINC01503 upregulated PD-L1 level by regulating miR-766-5p. Furthermore, rescue experiments showed that PD-L1 overexpression abrogated the inhibited impacts of blocking LINC01503 on CBP resistance in OCa cells. Conclusion GATA1-induced LINC01503 expedited CBP resistance in OCa cells via the miR-766-5p/PD-L1 axis, providing a new target for improving the efficacy of OCa chemotherapy. Graphical Abstract

Lnc-TMEM132D-AS1 as a potential therapeutic target for acquired resistance to osimertinib in non-small-cell lung cancer

“…[39][40][41][42] Besides, miR-766-5p is also involved in carboplatin resistance in ovarian cancer. 43 Our present study suggests for the first time that the expression and function of ENTPD1 can be modulated by lnc-TMEM132D-AS1 through the miR-766-5p sponge.…”

Pinpointing Functionally Relevant miRNAs in Classical Hodgkin Lymphoma Pathogenesis

“…Many studies have highlighted a role for miRNAs in regulating PD-L1 expression across various malignancies. Notably, various miRNAs downregulated in cHL, including miR-20b-5p, miR-34b, miR-138-5p, miR-148a-3p, miR-340-5p, miR-455-5p, and miR-766-5p, were shown to suppress PD-L1 expression in different cancer cell types [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. The downregulation of these miRNAs in cHL might contribute to the increased expression of PD-L1.…”

Differential effect of cancer-associated fibroblast-derived extracellular vesicles on cisplatin resistance in oral squamous cell carcinoma via miR-876-3p

“…Our present results revealed that CAFs strongly promote cancer progression and selectively suppress IGFBP3 expression via GATA1 transcriptional downregulation, which results in cisplatin resistance in OSCC. GATA1 was recently reported as involved in tumorigenesis, cancer progression 43 , 44 , and carboplatin resistance in ovarian cancer 45 . To date, there has been no data on the effect of GATA1 on cisplatin resistance.…”