Novel lncRNA UPLA1 mediates tumorigenesis and prognosis in lung adenocarcinoma

Xiaoyang Han,Hua Jiang,Yingying Tian,Wei Li,Jiamei Li,Qi Jing,Jinghan Yang,Jianni Qi,Chuanxi Wang

doi:10.1038/s41419-020-03198-y

Abstract

With the development of molecular biotechnology and sequencing techniques, long non-coding RNAs (lncRNAs) have been shown to play a vital role in a variety of cancers including lung cancer. In our previous study, we used RNA sequencing and high-content screening proliferation screening data to identify lncRNAs that were significantly associated with tumour biological functions such as LINC01426. Herein, based on previous work, we report a novel lncRNA UPLA1 (upregulation promoting LUAD-associated transcript-1), which has not been explored or reported in any previous studies. Our results showed that UPLA1 is highly expressed and regulates important biological functions in lung adenocarcinoma. In vitro experiments revealed that UPLA1 promoted the migration, invasion, and proliferation abilities, and is related to cell cycle arrest, in lung adenocarcinoma cells. Moreover, the upregulation of UPLA1 significantly improved the growth of tumours in vivo. We identified that UPLA1 was mainly located in the nucleus using fluorescence in situ hybridisation, and that it promoted Wnt/β-catenin signalling by binding to desmoplakin using RNA pulldown assay and mass spectrometry. Additionally, luciferase reporter assay revealed that YY1 is the transcription factor of UPLA1 and suppressed the expression of UPLA1 as a transcriptional inhibitor. This finding provides important evidence regarding the two roles of YY1 in cancer. Furthermore, in situ hybridisation assay results showed that UPLA1 was closely related to the prognosis and tumour, node, metastasis (TNM) stage of lung adenocarcinoma. In summary, our results suggest that the novel lncRNA UPLA1 promotes the progression of lung adenocarcinoma and may be used as a prognostic marker, and thus, has considerable clinical significance.

Highlights

Cancer is a primary public health problem and a major cause of death worldwide, and lung cancer is the principal cause of oncogenic mortality in both men and women[1,2]
LncRNA upregulation promoting LUAD-associated transcript-1 (UPLA1) is expressed in lung adenocarcinoma (LUAD) The analysis of four pairs of LUAD and normal tissue samples revealed differentially expressed long non-coding RNAs (lncRNAs) (Fig. 1A)
UPLA1 expression was examined in LUAD cell lines and normal lung bronchial epithelial cells using qRTPCR, and the results showed that UPLA1 was highly expressed in A549, H1299, and H1975 cells compared to BEAS-2B cells (Fig. 1E)

Summary

Introduction

Cancer is a primary public health problem and a major cause of death worldwide, and lung cancer is the principal cause of oncogenic mortality in both men and women[1,2]. There have been advances in radiotherapy, chemotherapy, and immunotherapy for lung cancer, its 5-year survival rate is still not satisfactory[4]. Genetic alteration is considered to be an important cause of tumorigenesis[5]. Based on efforts to regulate tumorigenesis at the genetic level, recent advances and epigenetic insights have suggested that long non-coding RNAs (lncRNAs) may be important tumour regulatory factors[6,7]. Several previous studies have identified important roles of lncRNAs in essential biological processes such as cellular proliferation, migration, and maintenance of pluripotency of stem cells, all of which are essential for tumour progression[9,10]. As regulators of LUAD pathogenesis, lncRNAs are considered as potential targets at the genetic level for cancer therapy and monitoring. Some lncRNAs, Official journal of the Cell Death Differentiation Association

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Results

Conclusion