Identification of a novel circ_0001946/miR‐1290/SOX6 ceRNA network in esophageal squamous cell cancer

Abstract

Background Circular RNAs (circRNAs) can function as competing endogenous RNAs (ceRNAs) to impact the development of esophageal squamous cell cancer (ESCC). Human circ_0001946 has been identified as a potential anticancer factor in ESCC, yet our understanding of its molecular basis remains limited. Methods Circ_0001946, microRNA (miR)‐1290 and SRY‐box transcription factor 6 (SOX6) were quantified by quantitative reasl‐time PCR (qRT‐PCR) or immunoblotting. Cell proliferation was assessed by CCK‐8 and EDU assays. Cell apoptosis and invasion were evaluated by flow cytometry and transwell assays, respectively. Cell migration was detected by transwell and wound‐healing assays. The direct relationship between miR‐1290 and circ_0001946 or SOX6 was determined by dual‐luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft model assays were used to assess the role of circ_0001946 in tumor growth. Results Circ_0001946 expression was attenuated in human ESCC, and circ_0001946 increase impeded cell proliferation, invasion, migration and enhanced apoptosis in vitro. Moreover, circ_0001946 increase diminished xenograft growth in vivo. Mechanistically, circ_0001946 bound to miR‐1290, and re‐expression of miR‐1290 reversed circ_0001946‐dependent cell properties. SOX6 was a miR‐1290 target and it was responsible for the regulation of miR‐1290 in cell properties. Furthermore, circ_0001946 functioned as a ceRNA to regulate SOX6 expression via miR‐1290. Conclusion Our findings uncover an undescribed molecular mechanism, the circ_0001946/miR‐1290/SOX6 ceRNA crosstalk, for the anti‐ESCC activity of circ_0001946.

Calycosin Inhibits the Malignant Behaviors of Lung Adenocarcinoma Cells by Regulating the circ_0001946/miR-21/GPD1L/HIF-1α Signaling Axis

“…Yao et al [ 13 ] reported that circ_0001946 was significantly upregulated in LUAD tumor tissues, but Zhang et al [ 22 ] found that the median expression level of circ_0001946 in NSCLC tissues was more than 3 times higher than that in tumor tissues. Besides, the expression of circ_0001946 in tumor tissues was also significantly lower than in tumor tissues in esophageal adenocarcinoma (ESCC) [ 23 ]. All in all, it is inconclusive whether circ_0001946 plays an anticancer or inhibitory role in malignant tumors since its expression may be affected by various factors.…”

MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma

“… MicroRNAs targeting the pathways of Wnt/β-catenin, IL6/Stat3, and TGF-β in esophageal squamous cell carcinoma metastasis. In esophageal squamous cell carcinoma (ESCC), miRNAs serve as crucial effector to Wnt/β-catenin, IL-6/STAT3 and TGF-β signalings, which is consistently involved in cancer metastasis[ 9 , 12 , 14 , 23 , 27 , 28 , 33 , 44 , 59 , 61 , 70 , 73 , 78 , 80 , 81 , 83 , 85 , 86 , 88 - 91 , 93 - 95 , 109 , 111 , 113 , 114 , 116 , 118 , 119 , 142 - 144 , 151 , 156 , 161 , 164 , 165 , 169 , 174 , 178 , 181 , 189 , 193 , 195 , 200 , 201 , 204 , 209 , 211 , 215 , 219 , 227 , 229 , 235 , 238 , 253 , 263 , 270 , 273 , 284 - 287 , 289 , …”

“…For example, both of miR-1269 and miR-1290 act as oncomiRs, and are upregulated in ESCC tissues and cell lines. They are associated with positive LNM and/or advanced TNM stage, and their overexpression promotes the malignant transformation of ESCC cells, including migration and invasion, by directly targeting SRY-box transcription factor 6, interactive with β-catenin (SOX6)[ 59 , 113 ]. Furthermore, the downregulation of miR-4429 has been shown to foster ESCC cell invasion and migration by partially regulating β-catenin through the direct targeting of SRXN1[ 114 ].…”

“…Recently, it was demonstrated that numerous circRNAs are differentially expressed in ESCC, and their dysfunction is linked to ESCC metastasis. The typical circRNAs contain circHIPK3, circ2646, circOGDH, circ_0001273, circABCB10, circ_0001946, circLARP4, circ_0007624, circFoxo3[ 25 , 71 , 100 , 113 , 136 - 140 ]. circ-OGDH was upregulated in ESCC cells and its inhibition repressed cell proliferation, migration, and invasion, and reduced miR-615-5p-induced cellular glutamine metabolism to regulate PDX1 expression[ 137 ].…”