Lung adenocarcinoma (LUAD) is the leading cause of cancer-related mortality worldwide. Long non-coding RNA (lncRNA) NUT family member 2A antisense RNA 1 (NUTM2A-AS1) is dysregulated in LUAD; however, its role in this disease remains unclear. The present study aimed to identify the underlying molecular mechanism of the effect of lncRNA NUTM2A-AS1 in LUAD by exploring whether lncRNA NUTM2A-AS1 could affect LUAD cell proliferation and apoptosis through the microRNA (miR)-590-5p/methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit (METTL3) axis. miR-590-5p was predicted and verified as the direct target of NUTM2A-AS1 using bioinformatics analysis and a dual luciferase reporter assay. The expression levels of NUTM2A-AS1 and miR-590-5p in lung cancer cells, and the effects of NUTM2A-AS1 on cell viability and apoptosis were determined using MTT assays and flow cytometry, respectively. Reverse transcription-quantitative PCR analysis revealed that the expression levels of NUTM2A-AS1 were significantly upregulated, while those of miR-590-5p were significantly downregulated, in lung cancer cells compared with the control epithelial cells. NUTM2A-AS1 knockdown inhibited NCI-H23 cell viability and induced apoptosis by upregulating miR-590-5p expression. Moreover, the function and regulatory mechanism of miR-590-5p in LUAD were also investigated. It was determined that miR-590-5p could interact with METTL3, and further analysis of the expression levels of METTL3 in lung cancer cells demonstrated that METTL3 was significantly upregulated in NCI-H23 and A549 cells compared with the control cells. In addition, miR-590-5p inhibited NCI-H23 cell viability and induced apoptosis by downregulating METTL3 expression. In conclusion, the findings of the present study suggested that NUTM2A-AS1 knockdown may inhibit LUAD progression by regulating the miR-590-5p/METTL3 axis. These results may provide insight into the mechanisms underlying the tumorigenesis of LUAD and offer a new treatment strategy for the disease.

Required for meiotic nuclear division 5 homolog A (RMND5A) functions as an E3 ubiquitin ligase. To date, few studies have investigated the role of RMND5A in cancer. In the present study, the expression levels of RMND5A in multiple types of cancer were analyzed using the Gene Expression Profiling Interactive Analysis platform. The results revealed that RMND5A was highly expressed and associated with overall survival in patients with pancreatic adenocarcinoma (PAAD). A wound-healing assay revealed that RMND5A overexpression significantly increased cell migration in the PAAD cell lines AsPC-1 and PANC-1. In silico analysis predicted that RMND5A was a potential target of microRNA(miR)-590-5p. Further in vitro experiments demonstrated that overexpression of miR-590-5p downregulated the expression levels of RMND5A and decreased the migratory ability of the AsPC-1 and PANC-1 cell lines. In addition, overexpression of miR-590-5p attenuated the promoting effects of RMND5A on the migration of AsPC-1 and PANC-1 cells. The results of the present study may further elucidate the mechanisms underlying PAAD progression and provide novel targets for the treatment of PAAD.

Recent studies have revealed that microRNAs (miRs) are involved in the pathogenesis of colorectal cancer (CRC); however, the roles of miR-590-5p in CRC are not completely understood. Therefore, the present study investigated the expression of miR-590-5p and programmed cell death 4 (PDCD4) in CRC tissues and healthy adjacent tissues via reverse transcription-quantitative PCR. Furthermore, human CRC cells were cultured in vitro and transfected with miR-590-5p inhibitor. CRC cell viability, migration and invasion were evaluated by conducting MTT, wound healing and Transwell assays, respectively. Additionally, the relative expression of PDCD4 and phosphorylated-Smad2/3 was analyzed via western blotting. miR-590-5p was significantly upregulated and PDCD4 was significantly downregulated in CRC tissues compared with healthy adjacent tissues. Moreover, the results indicated that miR-590-5p knockdown inhibited cell viability and migration by altering the expression of PDCD4, transforming growth factor-β and phosphorylated-Smad2/3. PDCD4 was identified as a direct target of miR-590-5p. In conclusion, the results of the present study suggested that miR-590-5p may regulate CRC cell viability and migration, indicating that miR-590-5p may serve as a potential therapeutic target for CRC.

Lung cancer with highest morbidity and mortality seriously threatens human health worldwide. Long noncoding RNAs (lncRNAs) exert important biological functions by acting as microRNA, which is implicated in tumorigenesis and cancer development. Previous work has reported that lncRNA-ATB expression was significantly upregulated in lung adenocarcinoma tissues and promoted tumor progression; however, the mechanisms of lncRNA-ATB in lung squamous carcinoma (LSC) are still fairly elusive. In our study, lncRNA-ATB expression also markedly increases in LSC tissues and cell lines in comparison to the adjacent normal tissues and normal lung epithelial cells, respectively. Functional experiments indicate that lncRNA-ATB overexpression improves the proliferative, migratory, and invasive capabilities of normal lung epithelial cells compared with control group. Furthermore, the migratory and invasive abilities are strikingly inhibited in lncRNA-ATB silenced LSC cells. Mechanistically, lncRNA-ATB directly binds to microRNA-590-5p and downregulates microRNA-590-5p level, leading to the upregulation of NF-90 expression. In addition, lncRNA-ATB overexpression promotes the epithelial-mesenchymal transition process, where lncRNA-ATB overexpression facilitates the expression of mesenchymal phenotype related molecules N-cadherin and vimentin, while restrains the expression of epithelial phenotype related proteins E-cadherin and CK-19, compared to the control. Conversely, microRNA-590-5p mimics can reverse the results caused by lncRNA-ATB overexpression. Taken together, our initial data suggest that lncRNA-ATB overexpression may promote the progression of LSC by modulating the microRNA-590-5p/NF-90 axis.

Non-small-cell lung cancer (NSCLC) is the leading type of cancer worldwide and sex determining region Y-box 2 (SOX2) has been implicated as an oncogene in various types of cancer. In the present study, SOX2 was positively associated with NSCLC stage and lymph node metastasis. Wound healing and Transwell assays demonstrated that knockdown of SOX2 inhibited A549 and H1299 cell migration. Furthermore, it was identified that knockdown of SOX2 inhibited epithelial-to-mesenchymal transition of NSCLC cells, which was demonstrated by increased expression of epithelial-cadherin and decreased expression of vimentin, zinc finger protein SNAI1 and zinc finger protein SNAI2. It was then demonstrated that SOX2 may be targeted by microRNA (miR)-590-5p, which indicated a potential therapeutic strategy for NSCLC focusing on the miR-590-5p/SOX2 axis.

OBJECTIVE: MicroRNA-590-5p (miR-590-5p) has been reported to stimulate osteoblast differentiation; however, its effect in diabetic osteoporosis remains unknown. This study investigated the effect of miR-590-5p on high glucose (HG)-suppressed osteoblast differentiation.
METHODS: The effect of HG on MC3T3-E1 cell survival was assessed using the MTT assay. The expression levels and activities of osteoblastic proteins were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR), alkaline phosphatase (ALP) assay, and immunoblotting assay. Tumor growth factor-β (TGF-β) signaling in MC3T3-E1 cells was assessed using luciferase assay, qRT-PCR, and immunoblotting. Mineralized nodule formation in MC3T3-E1 cells was examined by using the mineralization assay.
RESULTS: When MC3T3-E1 cells were exposed to HG conditions, there was significant downregulation of miR-590-5p and osteoblastic proteins (e.g., collagen I, Runx2, and ALP); in contrast, Smad7 was upregulated. Furthermore, miR-590-5p targeted Smad7 and inhibited its expression. Additionally, overexpression of miR-590-5p significantly promoted osteoblast growth and differentiation by upregulating TGF-β signaling in HG-treated MC3T3-E1 cells.
CONCLUSIONS: Collectively, the results showed that miR-590-5p was involved in osteogenesis; moreover, miR-590-5p may represent a potential target for the treatment of diabetic osteoporosis.

Breast cancer remains one of the foremost primary causes of female morbidity and mortality worldwide. During the current study, the effect of miR-590-5p and paired-like homeodomain transcription factor 2 (PITX2) on proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) of human breast cancer via the Wnt-β-catenin signaling pathway was investigated. Breast cancer-related genes and related signaling pathways were obtained from KEGG database. The PITX2 regulatory microRNA was predicted. To define the contributory role by which miR-590-5p influences the progression of breast cancer, the interaction between miR-590-5p and PITX2 was explored; the proliferation, invasion, and migration abilities as well as the tumor growth and metastasis in nude mice were detected following the overexpression or silencing of miR-590-5p. PITX2 was determined to share a correlation with breast cancer and miR-590-5p was selected for further analysis. PITX2, Wnt-1, β-catenin, N-cadherin, and vimentin all displayed higher levels, while miR-590-5p and E-cadherin expression were lower among breast cancer tissues than in the adjacent normal tissue. After overexpression of miR-590-5p or si-PITX2, the expression of E-cadherin was markedly increased, decreases in the expression of Wnt-1, β-catenin, N-cadherin, and vimentin, as well as inhibited cell proliferation, invasion, migration, metastasis, and EMT were observed. This study provides evidence suggesting that the transfection of overexpressed miR-590-5p can act to alleviate the effects of breast cancer demonstrating an ability to inhibit the processes of cell proliferation, migration, and invasion as well as EMT by suppressing the expression of PITX2 and activation of the Wnt-β-catenin pathway.

This study aimed to investigate the role of miR-590-5p in chondrocyte apoptosis and autophagy in response to mechanical pressure injury in vitro, as well as to elucidate its regulatory mechanism in the pathogenesis of osteoarthritis. We applied mechanical pressure of 10 MPa to chondrocytes for 60 minutes to establish the chondrocyte model of experimentally induced mechanical injury. We then investigated the expression of miR-590-5p in the injury model and the effects of miR-590-5p dysregulation on the expression of cell apoptosis-related and autophagy-related proteins. Cell apoptosis was detected by flow cytometry. Moreover, the potential targets of miR-590-5p were investigated. Mechanical pressure injury resulted in a significantly increased expression of miR-590-5p. Suppression of miR-590-5p significantly increased chondrocytes viability, inhibited chondrocytes apoptosis and autophagy in response to mechanical pressure injury. In addition, mechanical pressure injury led to a decreased expression of transforming growth factor β1 (TGFβ1). Moreover, TGFβ1 was confirmed as a direct target of miR-590-5p. Knockdown of TGFβ1 significantly induced chondrocytes apoptosis and autophagy in response to mechanical pressure injury, which was contrary to the effects of miR-590-5p suppression. Furthermore, overexpression of TGFβ1 and miR-590-5p at the same time significantly reversed the effects of overexpression of miR-590-5p alone on chondrocytes apoptosis and autophagy. Our results indicate that upregulation of miR-590-5p may target TGFβ1 to promote chondrocyte apoptosis and autophagy in response to mechanical pressure injury, thus contributing to the pathogenesis of osteoarthritis.

BACKGROUND: Resistance to chemotherapeutic treatment is a common phenomenon in cancers, especially in hepatocellular carcinoma (HCC). The Hippo signaling pathway has been demonstrated to play a role in tumor initiation, development, and progression. However, little is known about its roles in the HCC chemoresistance.
METHODS: In this study, real-time PCR and western blotting were used to identify the expression profile of key components of Hippo signaling pathway between chemoresistant and chemosensitive HCC cell lines. In vitro and in vivo loss- and gain-of-function studies were performed to reveal the effects and related mechanism of microRNA-590-5p/YAP1 axis in the chemoresistant phenotype of HCC cells.
RESULTS: We identified yes-associated protein 1 (YAP1) as the major dysregulated molecules in adriamycin (ADR)-resistant HCC cells. YAP1 was profoundly implicated in the chemoresistant phenotype of HCC cells. Furthermore, microRNA-590-5p was revealed as a functional modulator of YAP1. Importantly, YAP1-mediated chemoresistant phenotype was closely related to increased expression of stemness markers and ATP-binding cassette transporters. HCC patients with poor response to transarterial chemoembolization (TACE) treatment had higher protein level of YAP1 than that in the responsive patients.
CONCLUSIONS: The microRNA-590-5p/YAP axis plays an important role in the chemotherapeutic resistance of HCC cells, suggesting new adjuvant chemotherapeutic directions in HCC. FUND: National Natural Science Foundation of China, Zhejiang Province Medical and Health Care Key Project, Experimental Animal Science and Technology Projects of Zhejiang Province, Public Welfare Technology Application Research Project of Lishui, Chinese Medicine Science and Technology Projects of Zhejiang Province.