EGFR-AS1 Promotes Nonsmall Cell Lung Cancer (NSCLC) Progression via Downregulating the miR-524-5p/DRAM1 Axis and Inhibiting Autophagic Lysosomal Degradation.

Yang Xue,Xin Wang,Jing Zhang,Jiguang Hou,Xiangya Ding

doi:10.1155/2022/4402536

Abstract

Nonsmall cell lung cancer (NSCLC) accounts for the majority of lung cancers. Studies have revealed the regulatory role of lncRNAs in cancer pathogenesis and their potential use as diagnostic and prognostic biomarkers. The epidermal growth factor receptor antisense RNA 1 (EGFR-AS1) has been reported to be upregulated in NSCLC tissues, while its detailed mechanism in lung cancer needs to be explored. DNA damage-regulated autophagy modulator 1 (DRAM1) has been known to act as a tumor suppressor in NSCLC, and miR-524-5p has been reported to be a biomarker in idiopathic pulmonary fibrosis and different lung disorders. Our investigation revealed that EGFR-AS1 is highly expressed in lung cancer tissues, and its knockdown inhibited lung cancer cell invasion and viability and reduced tumor growth in vivo. We also found that EGFR-AS1 targets miR-524-5p, and there was a negative correlation between their expressions in lung cancer tissues. Simultaneously, miR-524-5p has been found to promote DRAM1 expression. In addition, the inhibition of miR-524-5p diminished DRAM1 protein expression and promoted lung cancer cell invasion. Our study has revealed that EGFR-AS1 contributes to the pathogenesis of NSCLC by inhibiting autophagic-lysosomal degradation via targeting the miR-524-5p/DRAM1 axis. This finding elucidated for the first time the role of EGFR-AS1 in lung cancer progression and the positive regulatory function of miR-524-5p in regulating DRAM1 protein and suppressing lung cancer progression. This novel mechanism provided a better insight into the pathogenesis of lung cancer and presented a better strategy for the treatment of lung cancer.

Highlights

Lung cancer is explicated as small cell lung cancer or nonsmall cell lung cancer (NSCLC), where NSCLC accounts for the majority of lung cancers and is a leading global cause of cancer-related deaths [1,2]
Cell Lines and Cell Culture. e human nontumorigenic lung epithelial cell line BEAS-2B was purchased from the American Type Culture Collection (ATCC) and was cultured in BEBM complete medium supplemented with 10% FBS and incubated at 37°C and 5% CO2 atmosphere along with penicillin (100 U/ml) and streptomycin (100 mg/ml, HyClone, USA). e adenocarcinoma lung cancer cell lines HCC827 and NCI-H1650 were purchased from ATCC and were cultured in RPMI-1640 medium supplemented with 10% FBS and incubated at 37°C and 5% CO2 atmosphere along with penicillin (100 U/ml) and streptomycin (100 mg/ ml, HyClone, USA) at 37°C with 5% CO2
EGFR-AS1 is upregulated in HCC827 and NCI-H1650 lung cancer cells compared to normal BEAS2B cells (Figure 1(a))

Summary

Introduction

Lung cancer is explicated as small cell lung cancer or nonsmall cell lung cancer (NSCLC), where NSCLC accounts for the majority of lung cancers and is a leading global cause of cancer-related deaths [1,2]. NSCLC is a heterogeneous disorder, with various subtypes representing different clinical indexes requiring different treatment strategies. Distinct clinical outcomes accompany these different histological subtypes, disclosing heterogeneity in disease aggressiveness and underlying prognostic alterations [3,4,5]. Complex cellular signaling and tumor microenvironment factors are associated with poor prognosis, imparting a distinctive biological basis to an individual’s disorder [1]. E identification of oncogenic driver modulations has helped ameliorate the outcomes in lung cancer patients. Most lung cancer patients do not have an actionable molecular abnormality [6,7]. Long noncoding RNAs (lncRNAs) are RNA transcripts larger than 200 bp and encode no proteins [8,9,10,11]. Long noncoding RNAs (lncRNAs) are RNA transcripts larger than 200 bp and encode no proteins [8,9,10,11]. lncRNA

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