Circular RNA circ-ZKSCAN1 inhibits bladder cancer progression through miR-1178-3p/p21 axis and acts as a prognostic factor of recurrence

Abstract

Background Circular RNAs (circRNAs) represent a subclass of regulatory RNAs that have been shown to have significant regulatory roles in cancer progression. However, the biological functions of circRNAs in bladder cancer (BCa) are largely unknown. Methods Cell invasion models were established, and invasion-related circRNAs were detected by qPCR. Using above method, circ-ZKSCAN1 was picked out for further study. Circ-ZKSCAN1 expression and survival analyses were performed through qPCR. The survival curves were generated by the Kaplan-Meier method, and the log-rank test was used to assess the significance. Cell proliferation, migration and invasion were examined to investigate the function of circ-ZKSCAN1. Tumorigenesis in nude mice was assessed to determine the effect of circ-ZKSCAN1 in bladder cancer. Biotin-coupled probe pull-down assays, FISH and luciferase reporter assays were conducted to confirm the relationship between circ-ZKSCAN1 and microRNA. RNA-seq revealed different molecular changes in downstream genes. Results Here, we found that circ-ZKSCAN1 was downregulated in BCa tissues and cell lines. Circ-ZKSCAN1 levels were associated with survival, tumor grade, pathological T stage and tumor recurrence. Overexpressed circ-ZKSCAN1 inhibits cell proliferation, migration, invasion and metastasis in vitro and in vivo. Mechanistically, we demonstrated that circ-ZKSCAN1 upregulated p21 expression by sponging miR-1178-3p, which suppressed the aggressive biological behaviors in bladder cancer. Conclusions These results reveal that Circ-ZKSCAN1 acts as a tumor suppressor via a novel circ-ZKSCAN1/miR-1178-3p/p21 axis, which have the important role in the proliferation, migration and invasion ablitities of BCa cells and provide a novel perspective on circRNAs in BCa progression.

RETRACTED ARTICLE: Hsa_circ_0001944 promotes the growth and metastasis in bladder cancer cells by acting as a competitive endogenous RNA for miR-548

“…Circ-ITCH inhibits BC progression by sponging miR-17/miR-224 and regulating p21 and PTEN expression [9]. Studies have also found that hsa_circ_0001361 [10], circPICALM [11], hsa_circ_0137606 [12], and circ-ZKSCAN1 [13] function in BC progression. Although many circRNAs are known to have significant functions in cancer, more work is needed to confirm their impact on cancer genetics.…”

Downregulated hsa_circ_0077837 and hsa_circ_0004826, facilitate bladder cancer progression and predict poor prognosis for bladder cancer patients

“…Bladder cancer (BC) belongs to the most commonly occurring malignancies of the urinary system and the ninth most frequently diagnosed cancer type with both high incidence and mortality rates worldwide 1,2 . Based on the depth of tumor infiltration, BC is categorized into muscle‐invasive bladder cancer (MIBC) (Ta, Tis, and T1, approximately accounting for 70%‐75%) and nonmuscle invasive bladder cancer (NMIBC) (T3‐T4, approximately 25%‐30%) 3‐5 . Of the patients with NMIBC, it has a higher recurrence rate after local tumor resection and is very likely to progress to MIBC 6 .…”

Hsa_circ_0001944 promotes the growth and metastasis in bladder cancer cells by acting as a competitive endogenous RNA for miR-548

“…Circ-ITCH inhibits BC progression by sponging miR-17/miR-224 and regulating p21 and PTEN expression [9]. Studies have also found that hsa_circ_0001361 [11], circPICALM [12], hsa_circ_0137606 [13], and circ-ZKSCAN1 [14] function in BC progression. Although many circRNAs are known to have signi cant functions in cancer, more work is needed to con rm their impact on cancer genetics.…”