lncRNA KLF3-AS1 Suppresses Cell Migration and Invasion in ESCC by Impairing miR-185-5p-Targeted KLF3 Inhibition

Abstract

Esophageal squamous cell carcinoma (ESCC) is a common cancer occurring in males and females worldwide. Accumulating evidence continues to highlight the crucial roles of long noncoding RNAs (lncRNAs) in the process of tumorigenesis. However, the regulatory mechanism of lncRNAs in ESCC remains unclear. The aim of this study is to elucidate the role of lncRNA Krüppel-like factor 3 antisense RNA 1 (KLF3-AS1) in ESCC by regulating miR-185-5p and KLF3. Initially, ESCC cell spheres with stem cell-like properties were prepared by suspension culture, and subsequently characterized by assessing colony formation ability and stem cell markers. LncRNA KLF3-AS1 was found to be poorly expressed in ESCC and could upregulate the expression of KLF3 by binding to miR-185-5p. lncRNA KLF3-AS1 upregulation was observed to inhibit miR-185-5p, thereby contributing to decreased expression of SOX2 and Oct4 (octamer-binding transcription factor 4). Furthermore, enhancement of lncRNA KLF3-AS1 resulted in reduced colony formation ability, cell invasion and migration, and tumor volume in vivo while promoting cell apoptosis in ESCC through downregulation of miR-185-5p. Collectively, this study indicated that lncRNA KLF3-AS1 inhibited ESCC cell invasion and migration by impairing miR-185-5p-mediated inhibition of KLF3, highlighting a promising novel potential target for ESCC treatment.

RETRACTED ARTICLE: Long noncoding RNA HEIH depletion depresses esophageal carcinoma cell progression by upregulating microRNA-185 and downregulating KLK5

“…HEIH was differentially expressed in EC, and participated in the occurrence and development of EC 9 , suggesting that HEIH may be a possible therapeutic target for the treatment of EC. miR-185-5p overexpression was able to inhibit the invasion and migration of ESCC cells 19 , and KLF5 was the core regulatory factor for ESCC cells 20 . Given that, we detected HEIH, miR-185, and KLK5 expression by RT-qPCR and western blot assay in cancer and non-tumoral tissues of EC patients, and found that HEIH and KLK5 were elevated, and miR-185 was declined in EC tissues vs non-tumoral tissues (Fig.…”

Silencing of lncRNA NEAT1 inhibits esophageal squamous cell carcinoma proliferation, migration, and invasion via regulation of the miR-1299/MMP2 axis

“…These results indicate that there is an ESCC-specific ceRNA network based on expression profiles of lncRNAs, miRNAs, and mRNAs [33]. Furthermore, similar ceRNA networks have been elucidated in numerous previous studies [10,12,14,16]. Collectively, these results strongly suggest that the supressed effect of lncRNA NEAT1 silencing on MMP2 in our present study was accomplished via the miR-1299 pathway.…”

“…For instance, lncRNA ZFAS1 is up-regulated in ESCC and promotes cell proliferation, migration, and invasion in ESCC cell lines by downregulating miR-124 and upregulating STAT3 [9]. lncRNA KLF3-AS1 is down-regulated in ESCC and inhibits tumor growth and invasion via weakening miR-185-5p-mediated inhibition of KLF3 [10]. lncRNA PANDA is upregulated in ESCC and drifts away from NF-YA to promote the expression of NF-YA-E2F1 co-regulated proliferation-promoting genes, as well as to restrict apoptosis [11].…”

LncRNA LINC00467 acted as an oncogene in esophageal squamous cell carcinoma by accelerating cell proliferation and preventing cell apoptosis via the miR‐485‐5p/DPAGT1 axis

“…In mechanism, although lncRNAs lack the capacity to encode proteins, they are able to regulate gene expression through direct or indirect mechanism 37 . Previous studies have demonstrated that lncRNA regulates target gene expression by acting as a molecular sponge for miRNA through the ceRNA pattern in the progression of ESCC 38–40 . The ceRNA pattern is a typical regulatory mechanism at the posttranscriptional level and refers to that lncRNA competitively binds with miRNAs to antagonize the suppressive effects of miRNAs on mRNAs 23 .…”