Cancer is the leading cause of death in humans, seriously hindering people's hopes for longevity. At the forefront is lung cancer (LC). Despite our understanding of the risk factors and pathogenesis of lung cancer, and some achievements in high-risk population screening, early diagnosis, personalized biomarkers, and drug development, the current situation of lung cancer is still not optimistic [1]. According to the Global Cancer Observatory (GLOBOCAN) project of the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO), the incidence and mortality of lung cancer have been steadily increasing in recent years. In 2012, there were approximately 1.8 million new cases of lung cancer and 1.6 million deaths worldwide. In 2018, there were 2.09 million new cases and 1.76 million deaths from lung cancer [2]. The latest data from 2022 show that there were 2.48 million new cases and 1.81 million deaths from lung cancer, making it still the leading cancer in terms of incidence and mortality [3]. In China, lung cancer tops the list of the five leading causes of death among citizens, accounting for 23.8 % of all cancer deaths [4]. These data indicate that lung cancer has always been an unsolved problem, and the continuously increasing incidence and mortality rates have brought significant social burdens to the country, making it an urgent social issue that needs to be addressed.
Lung cancer is a heterogeneous disease with widely varied clinical and pathological features. Broadly, it can be divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC far outnumbering SCLC cases, accounting for 85 % of all diagnoses [5]. Among NSCLC cases, lung adenocarcinoma (LUAD) has replaced squamous cell carcinoma as the most common histological subtype, constituting 60 % of new lung cancer cases, with its incidence still on the rise [6]. Therefore, the focus of lung cancer prevention and treatment cannot be separated from the prevention, diagnosis, and treatment of lung adenocarcinoma.
RNA transcripts that are more than 200 nucleotides in length and do not encode proteins are defined as lncRNAs [7]. Most lncRNAs are characterized by low abundance, and although their expression levels are usually lower than those of mRNAs, they show stronger tissue-specific expression patterns [8,9]. This suggests that lncRNAs play an integral role in cell type-specific processes [10]. Dysregulation of lncRNAs is a common feature of many human cancers, including lung cancer, and contributes to disease onset and progression [[11], [12], [13]]. In lung adenocarcinoma, different lncRNAs can play different roles in regulating key cellular processes such as cell proliferation [[14], [15], [16]], apoptosis [17,18], migration, invasion [[19], [20], [21]] and energy metabolism [20,22], which are hallmarks of cancer progression.
This study focuses on the association between lung adenocarcinoma and lncRNAs. By comparing the expression of upregulated lncRNAs in tumor tissues of lung adenocarcinoma patients with the surrounding normal lung tissues of patients with benign lung diseases using microarray screening, and then expanding the sample size of patients, while simultaneously validating in paired tumor patient samples and lung adenocarcinoma cell lines, lncRNA NR_146969 was found to be highly expressed in lung adenocarcinoma. According to the classification method based on genomic location, lncRNA NR_146969 belongs to intergenic lncRNAs, encoded as ENST00000449023, also known as SRGAP3-AS4. Based on the current level of research, the dysregulated expression of lncRNA NR_146969 in lung adenocarcinoma suggests a potential connection between the two. However, whether lncRNA NR_146969 regulates the malignant phenotype of lung adenocarcinoma cells and the regulatory association between them is still unknown. This undefined connection may provide new insights for further understanding the development, treatment, and prediction of patient prognosis in lung adenocarcinoma. Therefore, it is worth further research and exploration.
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