Reciprocal regulation of miR-1205 and E2F1 modulates progression of laryngeal squamous cell carcinoma

Pei Li,Xi-Jun Lin,Zi-Hao Xing,Meng-Ling Yuan,Jia-Rong Huang,Yao Li,An-Kui Yang,Xiao-Hui Yuan,Hui Liu,Meng-Ning Wei,Jin-Ming Di,Zhi Shi,Yang Yang,Jin Ye,Qi-Wei Jiang

doi:10.1038/s41419-019-2154-4

Abstract

The burgeoning functions of many microRNAs (miRs) have been well study in cancer. However, the level and function of miR-1205 in laryngeal squamous cell cancer remains unknown. In the current research, we validated that miR-1205 was notably downregulated in human laryngeal squamous cell carcinoma (LSCC) samples in comparison with tissues adjacent to LSCC, and correlated with T stage, lymph node metastasis, and clinical stage. Using Kaplan–Meier analysis indicates that high expression of miR-1205 has a favorable prognosis for patients with LSCC. Functional assays show that enforced miR-1205 expression attenuates the migration, growth, and invasion of LSCC cells. And E2F1 is verified to be a target of miR-1205, while E2F1 binds to miR-1205 promoter and transcriptionally inhibits miR-1205 expression. Overexpression of E2F1 reverses the inhibitory impacts of miR-1205 on LSCC cells in part. Importantly, E2F1 is abnormally increased in LSCC tissues, and its protein levels were inversely relevant to miR-1205 expression. High E2F1 protein level is in connection with clinical stage, T stage, lymph node metastasis, and poor prognosis. Consequently, reciprocal regulation of miR-1205 and E2F1 plays a crucial role in the progression of LSCC, suggesting a new miR-1205/E2F1-based clinical application for patients of LSCC.

Highlights

Laryngeal cancer is the14th most common malignancy worldwide in the male in contrast to that rarely in the female[1]
Downregulation of miR-1205 in Laryngeal squamous cell carcinoma (LSCC) is related to clinical stages, T stages, lymph node metastasis, and poor prognosis To explore the level of miR-1205 of LSCC tissues, a total 44 cases of LSCC samples and matching adjacent tissues were examined with real-time quantitative polymerase chain reaction (RT-qPCR)
We have validated that the level of miR-1205 is signally lower in clinical LSCC samples in comparison with corresponding adjacent tissues, and related to clinical stages, T stages, and lymph node metastasis

Summary

Introduction

Laryngeal cancer is the14th most common malignancy worldwide in the male in contrast to that rarely in the female[1]. Laryngeal squamous cell carcinoma (LSCC) occupies ~90% of all the larynx malignant tumors[3,4]. A profound and detailed understanding of the intrinsic molecular mechanisms underlying LSCC tumorigenesis and progression is urgently needed. MicroRNAs (miRs) are classical endogenous noncoding RNAs that usually play crucial regulatory parts in diverse physiological and pathological progresses through a posttranscriptional mechanism by sequence-specific binding with the 3′-untranslated regions (UTRs) of target genes[5]. Studies have shown that miRs serve as crucial roles in tumorigenesis and development of cancers. MiRs play the role of oncogenes or tumor suppressors by regulating their respective target genes, which are usually dysregulated in different types of cancer[6,7]. We have testified that the level of a novel miR1205 is notable decreased in tissues and cells of LSCC, and high-level miR-1205 suppresses the migration, Official journal of the Cell Death Differentiation Association

Methods

Results

Conclusion