Down expression of lnc-BMP1-1 decreases that of Caveolin-1 is associated with the lung cancer susceptibility and cigarette smoking history.

Lei Yang,Wenpeng Su,Xiaoxuan Ling,Huali Xiong,Xiaoxiao Lu,Jinbin Chen,Yinyan Li,Dongsheng Huang,Jiachun Lu,Jiansong Chen,Hongjun Zhao,Tiegang Li,Fuman Qiu,Yifeng Zhou,Chenli Xie,Binyao Yang,Di Wu

doi:10.18632/aging.102633

Abstract

Lnc-BMP1-1 is a lncRNA transcribed from SFTPC (surfactant associated protein C), a lung tissue specific gene encoding pulmonary-associated surfactant protein C (SPC) that is solely secreted by alveolar typeⅡ epithelial cells, among which the ones with SFTPC+ might be transformed into lung adenocarcinoma cells. Caveolin-1 (Cav-1) is a candidate tumor suppressor gene and is vital for coping with oxidative stress induced by cigarette smoke. When comparing lung cancer tissues with their adjacent normal tissues, the expression of lnc-BMP1-1 were decreased, especially in patients with cigarette smoking history (P=0.027), and positively associated with the expression of Cav-1 (P<0.001). When comparing to A549 cells transfected with empty vector (A549-NC cells), the expression level of Cav-1 in A549 cells with over-expressed lnc-BMP1-1 (A549-BMP cells) was increased along with the decreased level of HDAC2 protein. The drug sensitivity of A549-BMP cells to Doxorubicin hydrochloride (DOX) was increased; the growth and migration capability of A549-BMP cells were inhibited along with the decreased protein level of Bcl-2 and DNMT3a; the growth of tumor in nude mice injected with A549-BMP cells were inhibited, too. Furthermore, the lnc-BMP1-1 and Cav-1 expression was also down-regulated in the human bronchial epithelial (16HBE) cells treated with cigarette smoke extract (CSE).

Highlights

Long noncoding RNAs with lengths ranging from 200nt to 100 knt were termed as ‘transcribe noise’ decades ago
The clinical characteristics of the 276 patients with Lung cancer (LC) included in this study has been published in our previous studies conducted with the same subjects [39], another 17 patients were newly enrolled, the clinical characteristic of the study subjects are shown in Supplementary Table 2
There are promising biomarkers for lung cancer diagnosis, such as TTF1, folate receptor-positive circulating tumor cells [43, 44], but no Long noncoding RNAs (lncRNAs) are ready for broad clinical application [45], which calls for more exploration into the function and mechanism of lncRNAs

Summary

Introduction

Long noncoding RNAs (lncRNAs) with lengths ranging from 200nt to 100 knt were termed as ‘transcribe noise’ decades ago. They have been proven to be essential regulators of gene expression [1]. MALAT1 (Metastasis-associated lung adenocarcinoma transcript 1) and HOTAIR (HOX transcript anti-sense RNA) are well known lung cancer associated lncRNAs, with various functions in biological courses [3,4,5]. It is widely accepted that the functions of lncRNAs and the detailed mechanisms remain largely unexplored [7], which might be key issues for cancer research [8]

Methods

Results

Conclusion