LncRNA BLACAT1 Accelerates Non-small Cell Lung Cancer Through Up-Regulating the Activation of Sonic Hedgehog Pathway.

Lili Ge,Jiwei Sun,Wuying Yuan,Shu Liu,Xiao-Jun Liu,Liyue Ge,Jingzhou Jia,Wei Wang

doi:10.3389/fonc.2021.625253

Abstract

Recently, increasing evidence has displayed that lncRNAs can exhibit crucial function in cancer progression, including lung cancer. LncRNA bladder cancer-associated transcript 1 (BLACAT1) is reported to participate in various cancers. The aim of our current study was to investigate the function of BLACAT1 in non-small cell lung cancer progression and study the functional pathway. Here, we reported BLACAT1 was significantly up-regulated in lung cancer tissues in comparison to the adjacent normal tissues, which suggested BLACAT1 might act as an oncogene in lung cancer. Then, A549 and PC9 cells were infected with BLACAT1 overexpression plasmid and shRNA. As shown, we proved up-regulation of BLACAT1 greatly induced the growth of non-small cell lung cancer cells. Reversely, knockdown of BLACAT1 reduced A549 and PC9 cell proliferation, migration and invasion. Sonic hedgehog (shh) signaling is able to exert a significant role in carcinogenesis, including lung cancer. Currently, we proved that up-regulation of BLACAT1 activated shh signaling pathway, via inducing shh, Gli-1 and Smo expression. shh pathway inhibitor GANT-61 reversed the effect of overexpression of BLACAT1 on non-small cell lung cancer. Moreover, we manifested that loss of BLACAT1 remarkably reduced the in vivo growth and metastasis of A549 cells via enhancing infiltrating CD3+ T cells. In conclusion, our research revealed a critical role of BLACAT1 in the modulation of non-small cell lung cancer via modulating shh pathway.

Highlights

Lung cancer is a common cause of cancer-related death worldwide [1]
The significant data of our study is bladder cancer-associated transcript 1 (BLACAT1) demonstrates a crucial role in lung cancer development
We reported that BLACAT1 was significantly up-regulated in human lung cancer tissues

Summary

Introduction

Lung cancer is a common cause of cancer-related death worldwide [1]. Almost 1.4 million people have been diagnosed with lung cancer each year [2, 3]. NSCLC accounts for about 80–85% and SCLC accounts for 15–20%, respectively [4]. Advancing progress has been made in lung cancer, the overall survival rate of lung cancer still remains unfavorable [5]. A wide understanding of the possible mechanisms in non-small cell lung cancer is required.

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