Abstract
Several recent studies have shown that both strands of certain miRNAs derived from miRNA duplexes are involved in cancer pathogenesis. Our own recent studies revealed that both strands of the miR-150 duplex act as tumor-suppressive miRNAs in lung adenocarcinoma (LUAD) through the targeting of several oncogenes. The aim of the study here was to further investigate the tumor-suppressive roles of miR-150-3p (the passenger strand) in lung squamous cell carcinoma (LUSQ) and its control of cancer-promoting genes in LUSQ cells. The downregulation of miR-150-3p in LUSQ tissues was confirmed by data in The Cancer Genome Atlas (TCGA). The ectopic expression of miR-150-3p attenuated cancer cell aggressive features, e.g., cell cycle arrest, migration and invasive abilities. Our target search strategy successfully identified a total of 49 putative targets that were listed as subjects of miR-150-3p regulation in LUSQ cells. Interestingly, among these targets, 17 genes were categorized as related to the “cell cycle” based on Gene Ontology (GO) classification, namely CENPA, CIT, CCNE1, CCNE2, TIMELESS, BUB1, MCM4, HELLS, SKA3, CDCA2, FANCD2, NUF2, E2F2, SUV39H2, CASC5, ZWILCH and CKAP2). Moreover, we show that the expression of HELLS (helicase, lymphoid specific) is directly controlled by miR-150-3p, and its expression promotes the malignant phenotype of LUSQ cells.
Highlights
Lung cancer is the deadliest cancer in the world, and approximately 1.8 million patients died from this disease in 2018 [1,2]
The ordinately modulate oncogenic pathways, e.g., miR-28, miR-30a, miR-139, miR-143 and expression level of HELLS was determined to be independent prognostic factors in terms of miR-145 [27,28,34,35,36]. These findings show that several miRNA passenger strands are the 5-year overall survival rate after adjustments for age, sex, disease stage and pathological deeply associated with the molecular pathogenesis of human cancers
Ectopic expression assays demonstrated that miR-150-3p inhibited the aggressiveness of LUSQ cells, suggesting that miR-150-3p acts as a tumor suppressor
Summary
Lung cancer is the deadliest cancer in the world, and approximately 1.8 million patients died from this disease in 2018 [1,2]. Lung cancer is histologically categorized into two types: non-small cell lung cancer (NSCLC) and small cell lung cancer. 85% of all lung cancers are NSCLC, which is further classified into three subtypes: adenocarcinoma (LUAD), squamous cell carcinoma (LUSQ) and large cell carcinoma [3]. The latest genomic analyses have revealed the presence of therapeutic target genes for LUAD, e.g., EGFR, MET and BRAF mutations and RET, ALK and ROS1 rearrangements. Even with intensive genomic analysis using generation sequencing (NGS), the search for therapeutic targets for LUSQ has been difficult and is, an urgent task
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