Objective Our present research aimed to further investigate the molecular basis of long non-coding RNA homeobox A11 antisense (HOXA11-AS) in the tumorigenesis of non-small cell lung cancer (NSCLC)
Objective Our present research aimed to further investigate the molecular basis of long non-coding RNA homeobox A11 antisense (HOXA11-AS) in the tumorigenesis of non-small cell lung cancer (NSCLC). cells. And, DNMT1 upregulation weakened the influence of HOXA11-AS1 loss on NSCLC cell proliferation and apoptosis. Additionally, HOXA11-AS knockdown suppressed NSCLC xenograft growth by upregulating miR-148a-3p and downregulating DNMT1 in vivo. Conclusion HOXA11-AS facilitated NSCLC tumorigenesis through miR-148a-3p/DNMT1 Klf6 axis in vitro and in vivo, deepening our understanding of the molecular basis of HOXA11-AS in the development of NSCLC. Keywords: non-small cell lung cancer, tumorigenesis, HOXA11-AS, miR-148a-3p, DNMT1 Introduction Lung cancer is a huge threat for human health and life with an estimated 2.1 million new cases and 1.8 million deaths in 2018 alone worldwide.1 Moreover, the mortality and morbidity of lung tumor rates first in every malignancies.1 Non-small cell lung tumor (NSCLC), a significant histological subtype in lung tumor, makes up about approximately 85% of most instances.2,3 Regardless of the huge improvement within the administration of NSCLC, most NSCLC individuals are identified as having advanced or metastatic disease as well as the clinical results of current therapeutic strategies are unsatisfactory.4C6 Therefore, it really is of great importance to truly have a deep insight in to the etiologies of PT2977 NSCLC and look for potential biomarkers or targets for testing, analysis, prognosis, and treatment of NSCLC. Long non-coding RNAs (lncRNAs) having a length of much longer than 200 nucleotides (nt) and microRNAs (miRNAs) having a size around 20 nt certainly are a course of transcripts that absence protein-coding potential.7 Even though features of lncRNAs and miRNAs are uncharacterized largely, growing evidence shows that they may be mixed up in rules of gene expression and fundamental biological processes.8,9 Moreover, accumulating lncRNAs and miRNAs have been found to be central players in the development and progression of many diseases including cancers.10 LncRNA homeobox A11 antisense (HOXA11-AS), located on chromosome 7p15.2, has been reported to be abnormally expressed in multiple cancers, either as a tumor suppressor or an oncogenic factor.11,12 For instance, HOXA11-AS functioned as a tumor accelerator in breast cancer,13 hepatocellular cancer,14 and gastric cancer,15 whereas it exerted anti-tumor effects in glioblastoma,16 epithelial ovarian cancer,17 and colorectal cancer.18 Furthermore, previous studies showed that HOXA11-AS could promote the development and progression of NSCLC. 19C21 Bioinformatics examination showed that HOXA11-AS could possibly bind with miR-148a-3p. And, Sun et al demonstrated that HOXA11-AS could bind with PT2977 enhancer of zeste homolog 2 (EZH2) and argonaute 2 (Ago2), and EZH2 could interact with DNA methyltransferase 1 (DNMT1) in GC cells.15 Ago2 is a core component of RNA-induced silencing complex (RISC), which serves as a crucial player in miRNAs-mediated gene silence.22 Hence, we supposed that HOXA11-AS could regulate DNMT1 expression by some miRNAs. DNMT1 has been demonstrated to be a target of miR-148a-3p in some cancers such as laryngeal squamous cell cancer,23 and bladder cancer.24 And, Chen et al disclosed that miR-148a-3p inhibited DNMT1 expression in NSCLC cells.25 MiR-148a, miR-148b, and miR-152 are members of the miR-148/miR-152 family, which have been reported as multi-faceted role players in the development of normal, non-tumor, and tumor tissues.26,27 And, miR-148a has been found to be a potential tumor suppressor in many malignancies including NSCLC.28 These data suggested the link of HOXA11-AS, miR-148a-3p, and DNMT1. Consequently, we further explored whether HOXA11-AS could exert its functions through miR-148a-3p/DNMT1 regulatory axis in NSCLC. Our present study demonstrated that HOXA11-AS knockdown suppressed NSCLC cell proliferation and induced cell apoptosis in vitro and hampered NSCLC xenograft growth in vivo through upregulating miR-148a-3p and downregulating DNMT1. Materials And Methods Clinical Samples And Cell Culture A total of 36 NSCLC patients who underwent PT2977 surgical resection were enrolled in our project from Gansu Provincial Cancer.