Down‐regulation of long non‐coding RNA HOTAIR inhibits invasion and migration of oesophageal cancer cells via up‐regulation of microRNA‐204

Abstract

Oesophageal cancer is a progressive tumour with high mortality. However, therapies aimed at treating oesophageal cancer remain relatively limited. Accumulating studies have highlighted long non‐coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), microRNA‐204 (miR‐204) and homeobox C8 (HOXC8) in the progression of oesophageal cancer. Herein, we tried to demonstrate the function of HOTAIR, miR‐204 and HOXC8 in oesophageal cancer and their relationship. Differentially expressed genes involved in oesophageal cancer were identified. The endogenous expression of HOTAIR and miR‐204 in oesophageal cancer cell lines was altered to elucidate their effects and to identify the interaction among HOTAIR, miR‐204 and HOXC8. We also explored the underlying regulatory mechanisms of HOTAIR and miR‐204 with siRNA against HOTAIR, miR‐204 mimic or miR‐204 inhibitor. Cell proliferation, migration, invasion and apoptosis were subsequently detected. Xenograft in nude mice was induced to evaluate tumourigenicity. miR‐204 was down‐regulated, while HOTAIR and HOXC8 were up‐regulated in the oesophageal cancer tissues. HOTAIR could competitively bind to miR‐204 and miR‐204 could further target HOXC8. The oesophageal cancer cells treated with si‐HOTAIR or miR‐204 mimic exhibited decreased expression levels of HOXC8, Vimentin and MMP‐9, but increased E‐cadherin level. Silenced HOTAIR or elevated miR‐204 inhibited proliferation, migration and invasion, along with stimulated apoptosis of oesophageal cancer cells. In summary, our results show that lncRNA HOTAIR could specifically bind to miR‐204 as a competing endogenous RNA and regulate miR‐204 and HOXC8. Hence, down‐regulation of HOTAIR could inhibit progression of oesophageal cancer, indicating a novel target for oesophageal cancer treatment.

Long noncoding RNA LINC00324 promotes retinoblastoma progression by acting as a competing endogenous RNA for microRNA-769-5p, thereby increasing STAT3 expression

“…We also studied the regulatory mechanisms by which LINC00324 affects the malignant characteristics of RB cells in vitro and in vivo. Accumulated evidence suggests that lncRNAs perform their tumor-suppressive or oncogenic functions by interacting with certain miRNAs, and by attenuating the suppressive action of these miRNAs on the expression of their target genes [44][45][46]. Overall, the results of our study show that LINC00324 plays an oncogenic role in RB cells by functioning as a ceRNA for miR-769-5p, thereby upregulating STAT3.…”

<p>OIP5-AS1/miR-137/ZNF217 Axis Promotes Malignant Behaviors in Epithelial Ovarian Cancer</p>

“…4,5 Furthermore, dysregulated lncRNAs have been found to be correlated with tumor progression and poor prognosis outcome. 6,7 The competing endogenous theory has revealed that lncRNAs can function as a competing endogenous RNA (ceRNA) to bind with miRNA and reverse the inhibiting effect of the miRNA on target gene. Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1), a novel identified long intergenic noncoding RNA, has been studied in several cancers.…”

MicroRNA‐148a‐3p inhibits cancer progression and is a novel screening biomarker for gastric cancer

“…microRNAs (miRNAs) are a group of small noncoding RNAs which could regulate the post‐transcription expression level of their target genes 11,12 . Numerous studies have reported the close correlation between the aberrant expression of certain miRNAs and cancer progression 13,14 . For instance, miR‐193a‐3p was reported to regulate cisplatin resistance in CD44(+) gastric cancer cells 15 .…”