MiR-375/SLC7A11 axis regulates oral squamous cell carcinoma proliferation and invasion.

Yadong Wu,Xiaoling Qiu,Bin Song,Xiangjie Sun,Jianjiang Zhao

doi:10.1002/cam4.1110

Abstract

We aimed to detect the functions of miR‐375/SLC7A11 axis on oral squamous cell carcinoma (OSCC) cell proliferation and invasion. Expression levels of miR‐375 and SLC7A11 in OSCC tissues and cells were measured with RT‐qPCR and western blot. Targeting site was predicted by TargetScan and confirmed by dual luciferase reporting assay. By way of manipulating the expression level of miR‐375 and SLC7A11 in CAL‐27 and Tca8113 cell lines, the cell biological abilities were evaluated. MTT, colony formation, Transwell, wound healing assays and flow cytometry were used to detect OSCC cell viability, proliferation, invasion, migration and apoptosis, respectively. MiR‐375 was significantly downregulated in OSCC tissues and cells compared to adjacent tissue and normal oral cell line respectively while SLC7A11 was upregulated. Targeting relationship was verified by luciferase reporting assay, and miR‐375 could effectively suppress SLC7A11 level in OSCC cells. Replenishing of miR‐375 significantly repressed OSCC cell viability, proliferation, invasion and migration and induced cell apoptosis and G1/G0 arrest. Overexpression of SLC7A11 recovered those biological abilities in miR‐375 upregulated cells. Collective data suggested that miR‐375 served as a tumor suppressor via regulating SLC7A11. Replenishing of miR‐375 or knockout of SLC7A11 could be therapeutically exploited.

Highlights

Oral squamous cell carcinoma (OSCC) is perhaps the most prevalent type of head and neck cancer and it accounts for nearly 90% malignant oral tumor cases [1,2,3]
Oral squamous cell carcinoma is a high-risk cancer that afflicts a large number of populations and it threats the life of patients by local recurrence and metastatic neck lymph nodes [1,2,3, 29, 30]
The complex mechanisms of OSCC were widely studied and we found that SLC7A11 was upregulated in OSCC cells while the expression of miR-375 exhibited the opposite trend

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is perhaps the most prevalent type of head and neck cancer and it accounts for nearly 90% malignant oral tumor cases [1,2,3]. The 5-year survival rate of OSCC patients is approximately 60–80% which is reduced to 50% if OSCC is not diagnosed timely [3,4,5]. By base pairing to the 3’-UTR (Untranslated regions) of mRNA, miRNAs can downregulate their target mRNAs at the posttranscriptional level [7,8,9]. As suggested by several studies, miRNAs can function as biomarkers for the purpose of cancer screening, diagnosis and prognosis. Shin et al reported that miR-181a was downregulated in OSCC, indicating that miR-181a may function as an OSCC suppressor [10]. Sun et al found that both miR- 328 and miR-378 may trigger the brain metastasis of non-small-cell lung cancer; they may function as predictive biomarkers for diagnosing cancer progression [11].

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