Abstract

Emerging evidence has confirmed that long noncoding RNAs (lncRNAs) are strongly involved in tumor initiation and development. LncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) has been identified as a tumor facilitator in some cancers; nevertheless, its functional significance and regulatory mechanism remain greatly unclear in esophageal squamous cell carcinoma (ESCC). Here, we detected ZFPM2-AS1 expression in ESCC cell lines using qRT-PCR. ZFPM2-AS1 knockdown models were established for investigating the biological function of ZFPM2-AS1 in ESCC cells. The association between miR-3612 and ZFPM2-AS1 or TRAF4 was assessed by RNA pull-down and luciferase reporter assays. The present study indicated that ZFPM2-AS1 was significantly up-regulated in ESCC cells. Functional assays manifested that ZFPM2-AS1 knockdown restrained cell proliferation, migration and invasion, and facilitated cell apoptosis in ESCC. Mechanistically, ZFPM2-AS1 promoted ESCC cell growth and up-regulated TRAF4 to trigger NF-κB pathway by sequestering miR-3612. Besides, miR-3612 was confirmed to be a tumor inhibitor in ESCC. Through restoration experiments, we observed that TRAF4 overexpression could recover the suppressive effect of ZFPM2-AS1 on ESCC cell growth. Collectively, all the results suggested that ZFPM2-AS1 was an oncogene in ESCC cell growth by up-regulating TRAF4 and activating NF-κB pathway.

Highlights

  • Esophageal cancer, a commonly occurred cancer, causes the increasing deaths that related to cancers worldwide [1]

  • These findings suggested that ZFPM2-AS1 (NR 125796.1 but not NR 125797.1) is overexpressed in Esophageal squamous cell carcinoma (ESCC) and promotes ESCC cell growth

  • Accumulating studies have uncovered the aberrant expression of long noncoding RNA (lncRNA) in ESCC [22]

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Summary

Introduction

Esophageal cancer, a commonly occurred cancer, causes the increasing deaths that related to cancers worldwide [1]. It is of great importance to explore the novel biomarkers and mechanisms underlying ESCC progression for identifying attractive therapeutic strategies. LncRNA functions as a regulator in gene expression via multiple mechanisms, such as chromatin modifications, miRNA competition, protein amounts and genomic interactions [6,7]. LncRNA ZEB1-AS1 acts as an oncogene in glioma and promotes cancer progression [10]. LncRNA HULC promotes cell proliferation and invasion and activates PI3K/AKT pathway in pancreatic cancer [11]. SNHG6 [13] and LINC01980 [14] are up-regulated in ESCC and function as tumor promoter in ESCC progression. GAS5 [15] and FER1L4 [16] are down-regulated in ESCC and suppress the cancer progression.

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