LINC00261 Suppresses Cisplatin Resistance of Esophageal Squamous Cell Carcinoma Through miR-545-3p/MT1M Axis

Abstract

To improve the survival rate and cure rate of patients, it is necessary to find a new treatment scheme according to the molecular composition of (ESCC) in esophageal squamous cell carcinoma. Long non-coding RNAs (lncRNAs) regulate the progression of ESCC by various pathophysiological pathways. We explored the possible function of the lncRNA LINC00261 (LINC00261) on cisplatin (DDP) resistance of ESCC and its relative molecular mechanisms. In the study, we found that LINC00261 was downregulated in ESCC tissues, cell lines, and DDP-resistant ESCC patients. Besides, overexpression of LINC00261 not only inhibited cell proliferation, and DDP resistance but also promotes cell apoptosis. Further mechanistic research showed that LINC00261 sponged miR-545-3p which was negatively correlated with the expression of LINC00261. In addition, functional experiments revealed that upregulation of miR-766-5p promoted proliferation and enhanced DDP resistance. Subsequently, MT1M was testified to be the downstream target gene of miR-545-3p. Rescue experiments revealed that overexpression of MT1M largely restores miR-545-3p mimics-mediated function on ESCC progression. Our results demonstrate that the LINC00261 suppressed the DDP resistance of ESCC through miR-545-3p/MT1M axis.

The Role of Long Noncoding RNAs (lncRNAs) in Esophageal Cancer Therapy Resistance and Metastasis

“…Wang et al reported that LINC00261 expression was significantly lower in ESCC tissues and cells than in normal controls and that LINC00261 could negatively regulate miR-545-3p by sponging. Subsequently, metallothionein-1 M (MT1M), which was previously identified as a tumor suppressor [ 111 ], is targeted by miR-545-3p and is thus downregulated in ESCC tissues and cells, leading to resistance to cisplatin [ 112 ]. Moreover, in ESCC cells, CASC2 is expressed at low levels.…”

Roles of long non‑coding RNAs in esophageal cell squamous carcinoma (Review)

“…Furthermore, LINC00261, by modulating the miR-545-3p/metallothionein 1M axis, attenuated proliferation and cisplatin resistance, and promoted apoptosis in TE-1 and ECA109 cells ( 132 ). Transmembrane protein 161B-AS1, through miR-23a-3p/HIF1α inhibitor, inhibited proliferation, invasion and glycolysis of ECA109 and KYSE30 cells, with implications for TNM staging, lymph node metastasis and prognosis ( 133 ).…”

Current and future perspectives on the regulation and functions of miR-545 in cancer development

“… 42 Two lncRNA/miR-545-3p/PCG axes can suppress cancer progression, including the LINC01410/miR-545-3p/HK2 axis in neuroblastoma (NB) to suppress tumorigenesis and tumor radioresistance 5 and the LINC00261/miR-545-3p/MT1M axis to suppress cisplatin resistance in esophageal squamous cell carcinoma (ESCC) cell lines. 43 …”