Circular RNA ATXN7 promotes the development of gastric cancer through sponging miR-4319 and regulating ENTPD4

Abstract

Background: Circular RNAs (circRNAs) which are shown as a class of RNAs exhibit the importance in the regulation of gene expression and the development of biological process. However, the expression profile and molecular mechanism of circRNA ATXN7 (circATXN7) is still mostly uncertain in gastric cancer (GC). Methods: qRT-PCR analysis was performed to detect the expression of circATXN7, miR-4319 and ENTPD4 in GC tissues and cells. CCK-8, colony formation, EdU, flow cytometry, TUNEL and transwell assays were conducted to assess the effect of circATXN7 or miR-4319 on cell proliferation, apoptosis and invasion. In vivo assays were utilized to further analyze the function of circATXN7 on the tumorigenesis and progression of GC. The interaction between miR-4319 and circATXN7 (or ENTPD4) was verified using luciferase reporter and RNA pull-down assays. Results: The results showed an upregulated circATXN7 expression in GC tissues and cell lines. Besides, silenced circATXN7 hampered the proliferation and invasion as well as promoted the apoptosis in GC cells. Moreover, low expression of miR-4319 was found in GC. It was determined that circATXN7 acted as a sponge for miR-4319 and had a negative association with miR-4319. We also found that miR-4319 upregulation restrained GC cell proliferation and migration whereas enhanced apoptosis. Subsequently, ENTPD4, the target gene of miR-4319, was found overexpressed in GC. Additionally, it was negatively correlated with miR-4319 whereas positively associated with circATXN7. In vivo experiments, circATXN7 silence was confirmed to inhibit GC tumor growth. Conclusions: CircATXN7 promoted GC development through sponging miR-4319 and regulating ENTPD4, which identified circATXN7 as a new biomarker in GC.

RETRACTED: KCNQ1OT1 accelerates gastric cancer progression via miR-4319/DRAM2 axis

“…13 Here, we also showed miR-4319 was decreased expression in GC, and knockdown of miR-4319 stimulates GC cell growth, which is in consistent with the previous study result. 13 We also explored molecular mechanism by which KCNQ1OT1 regulates GC progression. We demonstrated KCNQ1OT1 interacts with miR-4319 to increase DRAM2 expression.…”

Circular RNA circ-MAT2B facilitates glycolysis and growth of gastric cancer through regulating the miR-515-5p/HIF-1α axis

“…Fox instance, circ-HIPK3 was shown to be upregulated in human colorectal cancer and promoted tumorigenesis and progression via sponging miR-7 and increasing the levels a series of protooncogenes [13]. And circ-ATXN7 was significantly increased in gastric cancer and expedited tumor growth via absorbing miR-4319 and elevating ENTPD4 [14].…”

The Biological Role of Sponge Circular RNAs in Gastric Cancer: Main Players or Coadjuvants?

“…They can also act as templates for protein translation and mediate immune responses [ 7 , 8 ]. Dysregulation in their role as miRNA-sponge has been reported in several types of gastrointestinal malignancies, including hepatocellular carcinoma [ 9 , 10 , 11 ], pancreatic [ 10 , 12 ], colorectal [ 10 , 11 , 13 ] and gastric cancer [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ,…”

“…A large number of studies have demonstrated the role of circRNAs as miRNA-sponges in GC [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. For example, it has been shown that alterations in circLARP4/miR-424/LATS1 [ ...…”