CircABCA13 acts as a miR‐4429 sponge to facilitate esophageal squamous cell carcinoma development by stabilizing SRXN1

Abstract

Circular RNAs (circRNAs) play a pivotal role in the tumorigenesis and progression of various cancers. However, the role and mechanisms of circABCA13 in esophageal squamous cell carcinoma (ESCC) are largely unknown. Here, we reported that circABCA13, a novel circular RNA generated by back‐splicing of the intron of the ABCA13 gene, is highly expressed in ESCC tumor tissues and cell lines. Upregulation of circABCA13 correlated with TNM stage and a poor prognosis in ESCC patients. While knockdown of circABCA13 in ESCC cells significantly reduced cell proliferation, migration, invasion, and anchorage‐independent growth, overexpression of circABCA13 facilitated tumor growth both in vitro and in vivo. In addition, circABCA13 directly binds to miR‐4429 and sequesters miR‐4429 from its endogenous target, SRXN1 mRNA, which subsequently upregulates SRXN1 and promotes ESCC progression. Consistently, overexpression of miR‐4429 or knockdown of SRXN1 abolished malignant behavior promotion of ESCC results from circABCA13 overexpression in vitro and in vivo. Collectively, our study uncovered the oncogenic role of circABCA13 and its mechanism in ESCC, suggesting that circABCA13 could be a potential therapeutic target and a predictive biomarker for ESCC patients.

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 , …”

“…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 ].…”

Biological functions of circRNA in regulating the hallmarks of gastrointestinal cancer (Review)

“…circ-0026611 is highly expressed in ESCC cells and exosomes, and exosomal circ-0026611 promotes ESCC lymphangiogenesis by interacting with N-α-acetyltransferase 10 and inhibiting prospero homeobox 1 acetylation and ubiquitination (55). High circABCA13 expression predicts a poor prognosis in patients with ESCC as it upregulates sulfiredoxin 1 and subsequently activates the Wnt/β-catenin pathway by acting as a sponge for miR-4429 in ESCC (56). Functional artificial circRNAs prevent miRNA binding to downstream target genes by adsorbing endogenous prooncogenic miRNAs, significantly inhibiting the growth and migration of EC cells, allowing a new avenue for the construction of therapeutic circRNAs (57).…”