Knockdown of circ-ABCB10 promotes sensitivity of lung cancer cells to cisplatin via miR-556-3p/AK4 axis

Abstract

Background Due to the acquired drug resistance, the potency of cisplatin-based chemotherapy is limited in lung cancer, which is a big obstacle in clinical treatment of lung cancer. Abundant evidence has revealed that circular RNAs (circRNAs) exerted facilitating or suppressive function on the tumorigenesis of multiple cancers. The oncogenic role of circ-ABCB10 in breast cancer and clear cell renal cell carcinoma has been validated in recent researches. However, the regulatory mechanism of circ-ABCB10 and its relation to cellular sensitivity to cisplatin in lung cancer is poorly understood. Methods The expression and characteristic of circ-ABCB10 were analyzed by RT-qPCR and nucleic acid electrophoresis. CCK-8, colony formation, TUNEL and transwell assays were applied to probe the role of FOXD3-AS1 in lung cancer. The interactions of miR-556-3p with circ-ABCB10 and AK4 were testified by luciferase reporter and RIP assays. Results Circ-ABCB10 was markedly upregulated and featured with loop structure in lung cancer. Circ-ABCB10 depletion suppresses lung cancer progression and sensitizes lung cancer cells to cisplatin. Molecular mechanism assays manifested that circ-ABCB10 bound with miR-556-3p and negatively modulated miR-556-3p expression. Additionally, AK4 was testified to be the downstream target of miR-556-3p. More importantly, rescue assays clarified that upregulation of AK4 could reverse the cisplatin-sensitizing and tumor-suppressing effect of circ-ABCB10 knockdown on lung cancer cells. Conclusions Circ-ABCB10 knockdown enhances sensitivity of lung cancer cells to cisplatin by targeting miR-556-3p/AK4 axis.

Circular RNA CHST15 Sponges miR-155-5p and miR-194-5p to Promote the Immune Escape of Lung Cancer Cells Mediated by PD-L1

“…CircRNAs were abnormally expressed in different cancers (9,11). In lung cancer, studies found that the expressions of hsa_circ_0072083, CircZNF124, and CircABCB10 are up-regulated (12,14,15) but that of hsa_circ_11780, CircPTK2, and hsa_circ_0078767 are down-regulated (13,17,18). This study discovered the up-regulation of CircCHST15 in lung cancer tissues and cells, which was similar to the findings of Liu et al (16).…”

“…In recent decades, evidence has increasingly proven that circRNAs play crucial parts in cancer development, including lung cancer (9)(10)(11). For example, CircZNF124 can promote the progression of nonsmall cell lung cancer cells by targeting mIR-337-3p (12); hsa_circ_0011780 inhibits the proliferation and metastasis of lung cancer (13); down-regulated CircABCB10 enhances the sensitivity of lung cancer cells to cisplatin (14); hsa_circ_0072083 could promote the effect of cisplatin on suppressing the growth of lung cancer (15). Furthermore, a recent study discovered that CircCHST15 (hsa_circ_0109320) is differentially expressed in gefitinib-treated lung cancer and might be a biomarker for the treatment of lung cancer in the future (16).…”

Circular RNAs act as regulators of autophagy in cancer

“…circ-ABCB10 (with 17 cricRNAD IDs, generated from ATP binding cassette subfamily B member 10) is a circRNA highly expressed in many cancers, including esophageal squamous cell carcinoma (ESCC), 43 oral squamous cell carcinoma, 44 lung cancer, 45 , 46 thyroid cancer, 47 BC, 48 and gliomas. 49 It acts as an oncogene by promoting cell proliferation, migration, and invasion while inhibiting cell apoptosis.…”

“… 49 It acts as an oncogene by promoting cell proliferation, migration, and invasion while inhibiting cell apoptosis. 43 , 44 , 45 , 46 , 47 , 48 , 49 circ-ABCB10 also plays an important role in the development of tumor drug resistance. 45 , 50 The knockdown of circ-ABCB10 could restore the sensitivity of DDP-resistant lung cancer cells and increase DDP-induced apoptosis by the miR-556-3p/AK4 axis.…”

“… 43 , 44 , 45 , 46 , 47 , 48 , 49 circ-ABCB10 also plays an important role in the development of tumor drug resistance. 45 , 50 The knockdown of circ-ABCB10 could restore the sensitivity of DDP-resistant lung cancer cells and increase DDP-induced apoptosis by the miR-556-3p/AK4 axis. 45 In BC cells, circ-ABCB10 knockdown could also increase the sensitivity of paclitaxel (PTX)-resistant cells to PTX and inhibit cell invasion.…”