Circ_0027599 elevates RUNX1 expression via sponging miR‐21‐5p on gastric cancer progression

Abstract

Background Increasing evidence has shown that circular RNAs (circRNAs) serve as vital regulators in tumour progression. In this study, we focused on the functions of circ_0027599 in gastric cancer (GC) progression. Methods The levels of circ_0027599, runt‐related transcription factor 1 (RUNX1) mRNA and microRNA‐21‐5p (miR‐21‐5p) were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR) assay. The protein levels of RUNX1, E‐Cadherin, vimentin and N‐Cadherin were measured by Western blot assay. Cell viability, colony formation, metastasis and cell cycle process were evaluated by Cell Counting Kit‐8 (CCK‐8) assay, colony formation assay, transwell assay and flow cytometry analysis, respectively. The interaction between circ_0027599 and miR‐21‐5p and the interaction between miR‐21‐5p and RUNX1 were verified by dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The role of circ_0027599 in tumour growth in vivo was investigated by murine xenograft model assay. Results Circ_0027599 and RUNX1 were downregulated in GC tissues and cells. Circ_0027599 level was associated with the overall survival of GC patients. Circ_0027599 or RUNX1 overexpression inhibited GC cell viability, colony formation, migration, invasion and cell cycle process in vitro. For mechanism analysis, circ_0027599 positively regulated RUNX1 expression via functioning as the sponge for miR‐21‐5p. RUNX1 inhibition reversed circ_0027599 overexpression mediated malignant behaviours of GC cells. Moreover, circ_0027599 overexpression repressed tumour growth in vivo. Conclusion Circ_0027599 overexpression repressed GC progression via modulation of miR‐21‐5p/RUNX1 axis, which might illumine a novel therapeutic target for GC.

Circular RNAs modulate Hippo-YAP signaling: functional mechanisms in cancer

“…In the last two decades, a large pool of studies has informed us about the roles of circRNAs in different types of cancers, whereby dysregulated expression of these circRNAs is reported to regulate various molecular entities as well as complex cell signaling cascades 28 , 135 , 136 . So far, several studies have highlighted the critical functions of circRNAs in altering basic tumor characteristics such as growth 137 , 138 , proliferation, invasion, migration, and metastasis 35 , 39 . In addition to these, their potential to be used as biomarkers and therapeutic targets have also been extensively elucidated in the field of cancer biology 21 , 139 .…”

Circ_SAR1A regulates the malignant behavior of lung cancer cells via the miR‐21‐5p/TXNIP axis

“…For instance, miR‐21‐5p was sponged by circ_PVT1 and participated in laryngeal cancer (LC) development. 35 Han et al 36 suggested that circ_0027599 could sponge miR‐21‐5p to inhibit gastric cancer progression; Jiang et al 37 revealed that miR‐21‐5p is up‐regulated in colorectal cancer (CRC) and is sponged by circEPB41L2; Li et al 38 illuminated that circPUM1 served as a sponge of miR‐21‐5p, promoting papillary thyroid cancer (PTC) tumorigenesis; Ma et al 39 verified that miR‐21‐5p bound to the 3′UTR of circ_ACAP2 to promote head and neck squamous cell carcinoma (HNSCC) cellular phenotypes. Another research by Yang et al 40 suggested that miR‐21‐5p is a target of circ‐LARP4, serving as an oncogene in lung cancer.…”

RUNX transcription factors: biological functions and implications in cancer

“…In a study of gastric cancer, Mitsuda et al demonstrated that elevated levels of RUNX1 in gastric cancer activated the ErbB2/HER2 signaling pathway by up-regulating SOS1, which served to promote the proliferation of gastric cancer cells [ 24 ]. However, the opposite conclusion has also been reached, namely, that RUNX1 is downregulated in gastric cancer tissues [ 57 ], suggesting a complex role of RUNX1 in the progression of this type of cancer. In hepatocellular carcinoma, elevated RUNX1 levels have been shown to upregulate COL4A1 expression, thereby activating the FAK-Src signaling pathway and promoting the proliferation, migration, and invasion of hepatocellular carcinoma cells [ 58 ].…”