ELOA promotes tumor growth and metastasis by activating RBP1 in gastric cancer.

BACKGROUND: Elongin A (ELOA), our previous work revealed, serves as a novel tumor suppressor in colorectal cancer. However, the function and mechanism of ELOA in other cancer types, including gastric cancer (GC), remain to be elucidated. METHODS: The expression of ELOA was measured by quantitative reverse transcription-polymerase chain reaction and western blot. The effects of ELOA on GC growth and metastasis were assessed through a series of in-vitro and in-vivo assays. Furthermore, the potential mechanism of ELOA was revealed by RNA sequencing, dual luciferase reporter assay, chromatin immunoprecipitation, and rescue experiments in GC. RESULTS: We uncovered increased expression of ELOA in GC tissues compared with paired normal tissues via bioinformatic analyses and our sample detection. Enhanced ELOA expression in GC tissues was obviously correlated with poor tumor differentiation, lymph node metastasis, advanced tumor stage, and a poor prognosis. A series of functional experiments showed that ELOA promoted the proliferation and metastasis of GC. Mechanistically, we revealed that the decreased levels of miR-490-3p caused the upregulation of ELOA in GC. Both RNA-seq and ChIP assays revealed that ELOA transcriptionally activated retinol-binding protein 1 (RBP1) by binding to its promotor. Furthermore, specific knockdown of RBP1 reduced the tumor-promoting ability of ELOA in GC cells. CONCLUSIONS: In summary, our findings demonstrate that ELOA exerts oncogenic properties by activating RBP1 expression, providing the basis for a promising therapeutic target in GC.

MiR-490-3p Sponged by lncRNA NEAT1 Can Attenuate Lung Adenocarcinoma Progression by Suppressing the RhoA/ROCK Signaling Pathway.

OBJECTIVE: Long noncoding RNAs (lncRNAs) are crucial regulators of lung adenocarcinoma (LUAD) progression. Herein, we explored the role of miR-490-3p and the underlying molecular mechanism involving key lncRNAs and pathways in LUAD. METHODS: Reverse transcription-quantitative PCR (RT-qPCR) was performed to detect the expression of lncRNA NEAT1 and miR-490-3p in LUAD cells and tissues. Western blotting was used to determine protein expression levels of the Ras homologous gene family member A/Rho-related protein kinase (RhoA/ROCK) signal pathway marker. Considering cell functions, Cell Counting Kit-8 (CCK-8), Transwell, and xenograft experiments were employed to evaluate LUAD cell proliferation, migration, and tumor growth, respectively. The relationship between miR-490-3p and lncRNA NEAT1 was analyzed using a luciferase reporter assay. RESULTS: Herein, we found that miR-490-3p expression was significantly low in LUAD cells and tissues. MiR-490-3p overexpression markedly suppressed tumor growth, the RhoA/ROCK signaling pathway, migration, and proliferation of LUAD cells. Moreover, lncRNA NEAT1, which is highly expressed in LUAD, was detected upstream of miR-490-3p. Upregulation of lncRNA NEAT1 exacerbated the behavior of LUAD cells and offset the suppressive influence of miR-490-3p-mediated upregulation on malignant LUAD cell behavior. CONCLUSION: MiR-490-3p sponging by lncRNA NEAT1 could hamper LUAD progression by inhibiting the RhoA/ROCK signaling pathway. These findings provide new insights for LUAD diagnosis and treatment.

High level of LncRNA MAPKAPK5-AS1 predicts poor prognosis and contributes to the malignant proliferation and EMT of non-small cell lung cancer via sponging miR-490-3p from HMGB2.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) show a low survival rate, owing to the lack of early diagnostic method and high invasiveness. Long non-coding RNA MAPKAPK5-AS1 that regulates tumor genesis and progression through multiple signals, is upregulated and involved in the growth and apoptosis in lung adenocarcinoma (LUAD). OBJECTIVE: To investigate whether MAPKAPK5-AS1 affected the malignant progression of NSCLC. METHODS: The levels of MAPKAPK5-AS1, miR-490-3p and HMGB2 in lung cancer were first analyzed through StarBase website, and confirmed by a quantitative reverse transcriptase-PCR (qRT-PCR) assay. The biological functions of NSCLC cells were examined by CCK-8, 5-ethynyl-2'-deoxyuridine (EdU) and flow cytometry assays. The potential binding sequences lncRNA-miRNA and miRNA-mRNA were predicted by StarBase software and verified via dual luciferase reporter experiment. The effects of MAPKAPK5-AS1 on tumor growth were evaluated in a xenografted mice model. RESULTS: The expression of MAPKAPK5-AS1 was upregulated in tumor tissues from NSCLC patients. Patients with high expression of MAPKAPK5-AS1 had higher tumor size, advanced TNM stage, higher incidence of lymph node and distant metastasis, and shorter overall survival. Knockdown of MAPKAPK5-AS1 inhibited the proliferation, induced apoptosis and blocked epithelial mesenchymal transformation (EMT) of NSCLC cells. Mechanically, MAPKAPK5-AS1 could upregulate the HMGB2 level in NSCLC cells through competitively binding to miR-490-3p. MiR-490-3p inhibitor reversed the roles of MAPKAPK5-AS1 knockdown on tumor cell proliferation, apoptosis and EMT. Also, HMGB2 knockdown suppressed tumor cell malignant phenotypes. Furthermore, interference of MAPKAPK5-AS1 slowed NSCLC tumor growth in vivo. CONCLUSION: Knockdown of MAPKAPK5-AS1 inhibited the aggressive tumor phenotypes through miR-490-3p/HMGB2 axis in NSCLC. MAPKAPK5-AS1/miR-490-3p/HMGB2 might be potential biomarkers or therapeutic targets for NSCLC.

Silencing of circCYP51A1 represses cell progression and glycolysis by regulating miR-490-3p/KLF12 axis in osteosarcoma under hypoxia.

Background: Hypoxia is a key characteristic of osteosarcoma (OS). Increasing data suggested that circular RNA (circRNAs) were involve in the progression of cancers and the regulation of hypoxia, including OS. This study aims to examine the biological mechanism of circRNA cytochrome P450 family 51 subfamily A member 1 (circCYP51A1) in OS under hypoxia. Methods: The expression levels of circCYP51A1, microRNA-490-3p (miR-490-3p) and kruppel-like factor 12 (KLF12) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in OS tissues and cells. Cell proliferation, migration and invasion were determined by colony formation assay and transwell assay. Lactate production and glucose consumption in OS cells were measured by using lactate assay kit and glucose assay kit, respectively. Western blot assay and immunohistochemistry assay were used to test protein levels. The associated relationship between miR-490-3p and circCYP51A1 or KLF12 was predicted using Starbase or DIANA online database and verified by dual-luciferase reporter assay. The xenograft model was used to explore the role of circCYP51A1 in vivo. Results: CircCYP51A1 and KLF12 expression were dramatically increased, whereas miR-490-3p was decreased in OS cells under hypoxia condition. Deficiency of circCYP51A1 hindered hypoxia-induced cell proliferation, migration, invasion and glycolysis in OS cells. CircCYP51A1 enhanced KLF12 expression by sponging miR-490-3p. MiR-490-3p inhibitor weakened the inhibition effect of circCYP51A1 knockdown on the progression of OS under hypoxia. Besides, overexpression of miR-490-3p inhibited cell progression of OS under hypoxia condition, while the effects were attenuated by KLF12 overexpression. Importantly, knockdown of circCYP51A1 inhibited tumor growth in vivo. Conclusion: CircCYP51A1 mediated cell proliferation, migration, invasion and glycolysis by regulating miR-490-3p/KLF12 axis in OS cells under hypoxia condition.

miR-490-3p Alleviates Cardiomyocyte Injury via Targeting FOXO1.

BACKGROUND: MicroRNA-490-3p (miR-490-3p) plays a role in the pathogeneses of a variety of cardiovascular diseases. Bioinformatic analysis showed that miR-490-3p was downregulated in the myocardial tissues of mice with myocardial infarction (MI). Nevertheless, the functions and mechanisms of miR-490-3p in MI remain unclear. METHODS: This study used an in-vitro model to investigate the role of miR-490-3p in MI. Human cardiac myocytes (HCMs) were cultured in a hypoxic environment. 3-(4,5)-Dimethylthiahiazo (-zy1)- 3,5-di-phenytetrazoliumromide (MTT) assay and flow cytometry were used to detect cell viability and apoptosis. The expression levels of forkhead box O1 (FOXO1) and miR-490-3p were detected by quantitative real-time PCR and Western blot. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), lactate dehydrogenase (LDH), cardiac troponin I (cTnI), and creatine kinase MB (CK-MB) were detected by enzyme-linked immunosorbent assay (ELISA). The targeted relationship between miR-490-3p and FOXO1 3'UTR was determined by a dual-luciferase reporter gene assay. RESULTS: miR-490-3p was significantly down-regulated in hypoxia-induced HCM cells, while FOXO1 was markedly up-regulated. miR-490-3p overexpression inhibited HCM cell inflammatory responses and injury after hypoxia treatment. FOXO1 was validated to be a direct target of miR- 490-3p, and its overexpression weakened the effects of miR-490-3p on cell viability, apoptosis, as well as inflammatory responses. CONCLUSION: miR-490-3p alleviates cardiomyocyte injury via targeting FOXO1 in MI.

LncRNA HCG11 Facilitates Nasopharyngeal Carcinoma Progression Through Regulating miRNA-490-3p/MAP3K9 Axis.

Purpose: Long noncoding RNAs (LncRNAs) play complex but important roles in the progression of various tumors. This study aimed to elucidate the functional mechanisms of the HLA complex group 11 (HCG11) in nasopharyngeal carcinoma (NPC). Patients and Methods: HCG11 levels in NPC specimens were determined by fluorescence in situ hybridization (FISH) and qPCR. Proliferation, apoptosis, and metastasis of NPC cells were determined using CCK8, colony formation, annexin V-PI, and transwell assays. A murine tumor xenograft model was used to investigate the regulatory function of HCG11 in NPC in vivo, and immunohistochemical staining was used to determine the Ki-67 level in tumors. The target relationships between HCG11, microRNA miR-490-3p, and MAPK kinase kinase 9 (MAP3K9) were detected using bioinformatics, qPCR, western blotting, and luciferase reporter assays. Results: HCG11 was highly expressed in NPC tissues and was positively associated with tumor stage, lymphatic metastasis, and poor prognosis. Functionally, HCG11 knockdown inhibited proliferation and migration and induced apoptosis of NPC cells. Mechanistically, miR-490-3p is a direct target of HCG11, oncogenic functions of HCG11 in NPC cell proliferation and migration can be partially reversed by the miR-490-3p inhibitor. HCG11 significantly increased mitogen-activated protein kinase MAPK kinase 9 (MAP3K9) levels by inhibiting miR-490-3p. Conclusion: HCG11 facilitates NPC progression via MAP3K9 signaling by sponging miRNA-490-3p, which may contribute to new prognostic markers and promising therapeutic targets.

CircXRCC5, as a Potential Novel Biomarker, Promotes Glioma Progression via the miR-490-3p/XRCC5/CLC3 Competing Endogenous RNA Network.

Circular RNAs (circRNAs), forming a covalently closed loop, are identified as a special subgroup of non-coding RNAs. Herein, we investigated the function and underlying mechanism of circXRCC5, generated from the XRCC5 gene, in glioma progression. Bioinformatics analysis was employed to determine the genomic information of circXRCC5 derived from XRCC5 pre-mRNA. Quantitative real-time PCR was conducted to examine the expression of circXRCC5 in glioma tissues and cells. Stable knockdown of circXRCC5 in U87 and U251 cells was established to assess its' biological functions. Cell Counting Kit-8, EdU incorporation, flow cytometry and transwell assay were performed to evaluate cell proliferation, apoptosis, migration and invasion, respectively. The circRNA-miRNA-mRNA regulatory network was verified using luciferase reporter assay and RNA immunoprecipitation. The samples were subjected to CHIP to ascertain the transcriptional regulation of XRCC5 at the promoter region of CLC3. Up-regulation of circXRCC5 was observed in glioma tissues and cell lines, and indicated poor prognosis of glioma patients. Knockdown of circXRCC5 suppressed cell proliferation, migration and invasion, while facilitated apoptosis. Mechanistically, circXRCC5 acted as a molecular sponge for miR-490-3p in a sequence-specific manner. There was a reciprocal negative feedback between circXRCC5 and miR-490-3p in an Argonaute2-dependent manner. Moreover, circXRCC5 acted as a sponge of miR-490-3p to regulate the expression of downstream target gene XRCC5, thus activating the transcription of CLC3, which fostered the progression of glioma. Collectively, circXRCC5 promoted glioma progression via the miR-490-3p/XRCC5/CLC3 ceRNA network, providing a novel prognostic biomarker and a prospective target for glioma treatment.

The regulation mechanism of LINC00707 on the osteogenic differentiation of human periodontal ligament stem cells.

The osteogenic differentiation of periodontal ligament stem cells (PDLSCs) is important for periodontal tissue repair and regeneration. Long non-coding RNAs (lncRNAs) are key regulators of diverse biological processes. However, their roles in PDLSC osteogenic differentiation are still largely unknown. This study explored the effect of LINC00707 and its mechanism on the osteogenic differentiation of human PDLSCs. Results showed an increase in LINC00707 and forkhead box O1 (FOXO1) but a decrease in miR-490-3p during PDLSC osteogenic differentiation. LINC00707 and FOXO1 promoted osteogenic differentiation as evidenced by the formation of calcium nodules and the increase in osteogenic markers such as alkaline phosphatase, osteocalcin (OCN), and runt-related transcription factor 2 (Runx2). LINC00707 and FOXO1 knockdown exhibited opposite effects. Dual-luciferase reporter assay and qRT-PCR showed that LINC00707 can specially bind to miR-490-3p, which reversed the effect of LINC00707 on PDLSCs. MiR-490-3p inhibitor relieved the inhibiting effect of sh-LINC00707 on osteogenic differentiation. Further investigation revealed that LINC00707 can promote osteogenic differentiation by regulating FOXO1 expression through miR-490-3p sponging. Thus, the LINC00707/miR-490-3p/FOXO1 axis modulated PDLSC osteogenic differentiation and might be a promising therapeutic target for periodontal diseases.

Role of miR-490-3p in blocking bladder cancer growth through targeting the RNA-binding protein PCBP2.

MiR-490-3p is regarded as a tumor suppressor in many cancers, but whether miR-490-3p is involved in the development of bladder cancer remains unknown. BALB/c nude mice (male, 15-20 g) were used to investigate the role of MiR-490-3p in bladder cancer. The relationship between miR-490-3p and PCBP2 involved in bladder cancer regulation were determined. Cell viability, proliferation, and cell cycle were estimated by cell counting kit-8 (CCK-8) assay, 5-bromo-2'-deoxyuridine (BrdU) detection, and flow cytometry analysis, respectively. In animal experiments, lentivirus was transfected into bladder cancer cells to overexpress miR-490-3p, which were then injected into mice and the change of tumor volume was assessed. Principal findings: The expression of MiR-490-3p was decreased in bladder cancer cells. Overexpression of miR-490-3p inhibited bladder cancer cell viability and proliferation. Moreover, overexpression of miR-490-3p caused cell cycle arrest in bladder cancer cells. The inhibitory effect of miR-490-3p on bladder cancer cells growth could be counteracted by enhancing PCBP2 expression. In vivo, bladder cancer growth in mice was blocked by miR-490-3p upregulation. MiR-490-3p suppressed bladder cancer growth and bladder cancer cell proliferation by down-regulating PCBP2 expression.

LINC00958 promotes bladder cancer carcinogenesis by targeting miR-490-3p and AURKA.

BACKGROUND: Bladder cancer is a prevalent malignancy of the urinary system, in which long non-coding RNAs (lncRNAs) are highly associated. We aimed to elucidate the role of LINC00958 in bladder cancer. METHODS: LINC00958 expression levels were measured using qRT-PCR. The interaction of LINC00958-miR-490-3p-AURKA was analyzed by luciferase, RIP, and RNA pull-down assays. The biological roles of LINC00958, miR-490-3p, and AURKA in bladder cancer cells were analyzed using CCK8, BrdU, and transwell assays. RESULTS: Increased expression of LINC00958 and AURKA was observed in bladder cancer tissues and cell lines. Decreased LINC00958 expression repressed bladder cancer progression and downregulation of miR-490-3p accelerated bladder cancer cell progression. Moreover, LINC00958 sponges miR-490-3p to upregulate AURKA expression, thereby promoting carcinogenesis in bladder cancer cells. CONCLUSIONS: Our study revealed that LINC00958 facilitated cell proliferation and invasion, and suppressed cell apoptosis by sponging miR-490-3p and upregulating AURKA, thus inspiring a new treatment method for bladder cancer.

RNA-Sequencing Based microRNA Expression Signature of Colorectal Cancer: The Impact of Oncogenic Targets Regulated by miR-490-3p.

To elucidate novel aspects of the molecular pathogenesis of colorectal cancer (CRC), we have created a new microRNA (miRNA) expression signature based on RNA-sequencing. Analysis of the signature showed that 84 miRNAs were upregulated, and 70 were downregulated in CRC tissues. Interestingly, our signature indicated that both guide and passenger strands of some miRNAs were significantly dysregulated in CRC tissues. These findings support our earlier data demonstrating the involvement of miRNA passenger strands in cancer pathogenesis. Our study focused on downregulated miR-490-3p and investigated its tumor-suppressive function in CRC cells. We successfully identified a total of 38 putative oncogenic targets regulated by miR-490-3p in CRC cells. Among these targets, the expression of three genes (IRAK1: p = 0.0427, FUT1: p = 0.0468, and GPRIN2: p = 0.0080) significantly predicted 5-year overall survival of CRC patients. Moreover, we analyzed the direct regulation of IRAK1 by miR-490-3p, and its resultant oncogenic function in CRC cells. Thus, we have clarified a part of the molecular pathway of CRC based on the action of tumor-suppressive miR-490-3p. This new miRNA expression signature of CRC will be a useful tool for elucidating new molecular pathogenesis in this disease.

LncRNA CCAT1 promotes prostate cancer cells proliferation, migration, and invasion through regulation of miR-490-3p/FRAT1 axis.

Prostate cancer (PCa) is a prevalent cancer in males, with high incidence and mortality. Recent studies have shown the crucial role of long non-coding RNA (lncRNA) in PCa. Here, we aimed to explore the functional roles and inner mechanisms of lncRNA CCAT1 in PCa cells. qRT-PCR results showed that CCAT1 was upregulated in PCa tissues and cells. Functional assays demonstrated that CCAT1 knockdown suppressed cell proliferation, migration, invasion, yet promoted apoptosis, while CCAT1 promotion showed the opposite results. We also found that CCAT1 negatively regulated miR-490-3p expression and subsequently regulated FRAT1 expression. Inhibition of miR-490-3p or up-regulation of FRAT1 reversed the suppressive effects of CCAT1 knockdown on the PCa cells. In conclusion, CCAT1 regulated FRAT1 expression through miR-490-3p and then promote the PCa cells proliferation, migration, and invasion, which reveals the oncogenic function of CCAT1 in PCa progress.

LncRNA CCDC144NL-AS1 Serves as a Prognosis Biomarker for Non-small Cell Lung Cancer and Promotes Cellular Function by Targeting miR-490-3p.

This study revealed the prognostic significance of long non-coding RNA (lncRNA) CCDC144NL-AS1 in NSCLC patients and discussed the effect and mechanism of proliferation, migration, and invasion of non-small cell lung cancer (NSCLC) cells. 128 pairs of NSCLC tissues and paracancerous tissues were collected, and qRT-PCR was used to detect the differential expression of lncRNA CCDC144NL-AS1 in all tissues and cells lines. Kaplan-Meier analysis and Cox proportional hazards model analysis were used to estimate the prognostic value of lncRNA CCDC144NL-AS1. CCK-8 and Transwell assays confirmed the effect of lncRNA CCDC144NL-AS1 on the proliferation, migration, and invasion of NSCLC. Bioinformatics was used to predict the microRNAs that lncRNA CCDC144NL-AS1 might bind to miR-490-3p. The regulation of lncRNA CCDC144NL-AS1 on miR-490-3p was verified by luciferase activity assay with wide type or mutation. The expression of lncRNA CCDC144NL-AS1 was enhanced in both NSCLC tissues and cell lines. Patients with overexpression of lncRNA CCDC144NL-AS1 have a poor prognosis, and lncRNA CCDC144NL-AS1 is an independent prognostic factor for NSCLC. Increased the relative expression level of lncRNA CCDC144NL-AS1 can promote the proliferation, migration, and invasion of NSCLC cells. LncRNA CCDC144NL-AS1 might target miR-490-3p. LncRNA CCDC144NL-AS1 can be used as an oncogene of NSCLC to predict patient prognosis and promote tumor proliferation, migration, and invasion by targeting miR-490-3p.

Long non-coding RNA AL139002.1 promotes gastric cancer development by sponging microRNA-490-3p to regulate Hepatitis A Virus Cellular Receptor 1 expression.

Mounting evidence suggests that lncRNA regulates many important diseases. However, the biological role of most lncRNAs in gastric cancer (GC) remain unclear. In this paper, we determined differential expression of lncRNAs and predicted ceRNA networks in the GC database by bioinformatics analysis and validated in GC cells. The effect of lncRNA AL139002.1 on GC cells biological function was assessed by flow cytometry, CCK-8, colony formation, wound healing assay, transwell, western blot, and qRT-PCR. And the relationship of lncRNA AL139002.1 or HAVCR1 with miR-490-3p was verified by luciferase reporter assay. The results showed that lncRNA AL139002.1 was highly expressed in GC cells and lncRNA AL139002.1 knockdown induced apoptosis, while suppressed cell proliferation, migration, invasion, and EMT. Functional examining indicated that lncRNA AL139002.1 regulated HAVCR1 expression by competitively binding miR-490-3p. In addition, lncRNA AL139002.1/miR-490-3p/HAVCR1 regulated EMT and metastasis through MEK/ERK signaling. In conclusion, lncRNA AL139002.1 was highly expressed in GC cells, and lncRNA AL139002.1/miR-490-3p/HAVCR1 functioned critically in GC by regulating MEK/ERK signaling. Our findings demonstrated that lncRNA AL139002.1 served as a potential therapeutic and anti-metastatic biotarget for GC.

MiR-490-3p Silences CDK1 and Inhibits the Proliferation of Colon Cancer Through an LLPS-Dependent miRISC System.

Liquid-liquid phase separation (LLPS) is a burgeoning concept in cell biology, which was associated with miRISC machinery. However, most studies about LLPS are based on overexpression of core proteins, which is far away from nature condition of cells, whether miRISC underwent LLPS under biological condition remains unknown. Taking miR-490-3p and its target CDK1 as an example, we revealed without overexpression of any protein components, miRISC functioned in an LLPS-depend manner. We firstly found miRISC has liquid-like properties in colon cancer (CC) cells and could fulfill common LLPS criteria under overexpression condition. Then, RIP was performed to confirm miR-490-3p is actually functioning in miRISC. RT-qPCR, western blot and luciferase assays were performed and found miR-490-3p could significantly decrease expression of CDK1 in both RNA and protein levels. However, without overexpression of miRISC components, when treating CC cells with 1,6-hexanediol(1,6-HD), a widely used LLPS inhibitor, the silence effects of miR-490-3p to CDK1 were totally abolished, no matter in RNA, protein or luciferase levels, suggesting that miRISC functions in an LLPS-depend way under biological condition. In conclusion, we found miR-490-3p could silence CDK1 to inhibit the proliferation of CC cells in an LLPS-depend manner.

MicroRNA-490-3p inhibits migration and chemoresistance of colorectal cancer cells via targeting TNKS2.

OBJECTIVE: Colorectal cancer is one of the most common malignancy in the world. The oncogenesis of colorectal cancer is still not fully elucidated. It was reported that microRNA-490-3p (miR-490-3p) was closely related to the regulation of cancers. However, if miR-490-3p could also affect colorectal cancer and the specific mechanism remains unclear. METHODS: qRT-PCR was conducted to examine the expression of miR-490-3p. DIANA, miRDB, and TargetScan databases were used to identify target genes. LOVO and SW480 cells were transfected by miR-490-3p mimics and inhibitors. Transwell assay was used to measure cell invasion and migration. Cisplatin and fluorouracil were administered to investigate chemotherapy resistance. Western blot was used to measure TNKS2 protein expression. Binding sites were verified using the double luciferase assay. RESULTS: miR-490-3p expression was low in the colorectal cancer cells. The level of miR-490-3p was negatively correlated with cell migration and invasion of cancer cells. miR-490-3p could bind to TNKS2 mRNA 3'UTR directly. miR-490-3p can suppress cell viability and resistance to chemotherapy in colorectal cancer cells through targeting TNKS2. CONCLUSIONS: miR-490-3p could affect colorectal cancer by targeting TNKS2. This study may provide a potential therapeutic target for colorectal cancer.

miRNA­490­3p promotes the metastatic progression of invasive ductal carcinoma.

MicroRNA (miRNA/mir)­490­3p has been defined as a tumor suppressor in different types of cancer, including breast cancer. However, miR­490­3p has been shown to function as a tumor suppressor and promoter in a context­dependent manner in hepatocellular and lung cancer. Contrary to previous studies, the present study revealed that miR­490­3p expression was significantly higher in invasive ductal carcinoma (IDC) tissue specimens, the most common form of breast cancer, compared to tumor­adjacent normal tissue specimens (n=20). Its expression was also higher in the more metastatic breast cancer cell line, MDA­MB­231, compared to the non­metastatic breast cancer cell line, MCF7, and the moderately metastatic breast cancer cell line, MDA­MB­468. The expression of miR­490­3p was induced following transforming growth factor (TGF)­ß­induced epithelial­to­mesenchymal transition (EMT) in MCF10A cells. Gain­and loss­of­function assays revealed that the expression of miR­490­3p regulated the proliferation, colony formation, EMT, migration and invasion in vitro, but not the apoptosis of MDA­MB­468 and MDA­MB­231 cells. The knockdown of miR­490­3p expression in MDA­MB­231 cells inhibited experimental metastasis in a tumor xenograft assay. As in lung cancer, miR­490­3p was found to target and downregulate the expression of the tumor suppressor RNA binding protein poly r(C) binding protein 1 (PCBP1). PCBP1 protein and miR­490­3p expression inversely correlated in patients with ductal carcinoma in situ (DCIS; n=10; no nodal involvement) and IDC (n=10; different stages of metastatic progression) with a significantly higher miR­490­3p expression in patients with IDC compared to those with DCIS. The expression of miR­490­3p was negatively associated with both overall and disease­free survival in the patients with breast cancer included in the present study. On the whole, the results confirm a pro­metastatic role of miR­490­3p in IDC, establishing it as a biomarker for disease progression in these patients.

Long noncoding RNA-SNHG20 promotes silica-induced pulmonary fibrosis by miR-490-3p/TGFBR1 axis.

Silicosis is a universal occupational disease, which is caused by long-term crystalline silica exposure. Recent studies have shown that noncoding RNAs participate in diverse pathological cellular pathways. However, the precise regulation mechanism remains limited in silicosis. Here, we established a silica-induced mouse fibrosis model (all mice received a one-time intratracheal instillation with 50 mg/kg of silica in 0.05 mL sterile saline). MiR-490-3p was significantly downregulated in silica-induced fibrotic mouse lung tissues and TGF-ß1 treated fibroblasts. Moreover, overexpressed miR-490-3p could relieve silica-induced lung fibrosis in vivo, and prevent the process of fibroblast-to-myofibroblast transition(FMT)in vitro. Mechanistically, TGFBR1 was one of the major target genes of miR-490-3p, and tightly associated with the process of fibroblasts activation. SNHG20, as opposed to miR-490-3p expression, was elevated in TGF-ß1-treated fibroblast cell lines and contributed to decreased levels of miR-490-3p. Taken together, these data indicated that miR-490-3p plays a key role in silica-induced pulmonary fibrosis. Our results suggested that SNHG20/miR-490-3p/TGFBR1 axis may provide a new treatment target of pulmonary fibrosis.

MiR-490-3p Inhibits the Malignant Progression of Lung Adenocarcinoma.

OBJECTIVE: To investigate the effects of miR-490-3p on the proliferation, migration, invasion and apoptosis of lung adenocarcinoma (LUAD) cells through the Wnt/ß-catenin signaling pathway. METHODS: Differentially expressed miRNAs in LUAD tissues were analyzed by bioinformatics and the target miRNA went through GSEA enrichment analysis. qRT-PCR was used to detect the expression of miR-490-3p in human LUAD cells and normal bronchial cells. The constructed vectors were transfected into the LUAD cell lines using Lipofectamine 2000. Cell viability was detected by MTT, cell migration and invasion were detected by transwell assay, and cell apoptosis was detected by flow cytometry. Western blot was performed to detect the expression levels of the proteins related to the Wnt/ß-catenin pathway and cell apoptosis. Xenograft tumor mouse models were used for in vivo validation. RESULTS: The results of qRT-PCR showed that miR-490-3p was relatively lowly expressed in LUAD cells, and the expression level was different in different LUAD cell lines. The results of MTT, transwell and flow cytometry exhibited that miR-490-3p could significantly inhibit the proliferation, migration, invasion and increase cell apoptosis rate of LUAD cells. Western blot results showed that miR-490-3p promoted the expression of Bax, Caspase-3 and E-cadherin as well as the phosphorylation of GSK-3ß and inhibited the expression of Bcl-2, ß-catenin and C-myc. Additionally, animal experiments were performed to prove that miR-490-3p suppressed LUAD malignant progression in vivo. CONCLUSION: MiR-490-3p inhibited the proliferation, migration, invasion and promoted the apoptosis of LUAD cells by down-regulating the Wnt/ß-catenin signaling pathway, suggesting that miR-490-3p may be an indicator for early diagnosis and prognosis of LUAD.

MicroRNA-490-3p suppresses the proliferation and invasion of hepatocellular carcinoma cells via targeting TMOD3.

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. It has been reported that microRNAs (miRs) play important roles in the progression and development of HCC. The expression of miR-490-3p has been shown to be downregulated in HCC tissues. Therefore, the present study aimed to investigate the effects of miR-490-3p on HCC cells and the underlying mechanism. Cell Counting Kit-8, flow cytometry, and Transwell migration and invasion assays were performed to determine the viability, apoptosis, migration and invasion of HCC cells, respectively. Furthermore, a luciferase activity assay was used to verify the association between miR-490-3p and its predicted target tropomodulin 3 (TMOD3). In addition, the protein levels of Bax, Bcl-2, cleaved caspase-3, TMOD3, phosphorylated (p)-p38 and p-ERK in HCC cells were detected using western blot analysis. The results demonstrated that the overexpression of miR-490-3p via transfection with miR-490-3p mimics significantly inhibited the proliferation of Huh-7 and HEP 3B2.1-7 cells. In addition, overexpression of miR-490-3p markedly suppressed the migration and invasion abilities of Huh-7 cells. miR-490-3p mimics significantly induced liver cancer cell apoptosis via upregulating Bax and cleaved caspase-3 and downregulating anti-apoptotic protein Bcl-2. Additionally, a luciferase activity assay indicated that TMOD3 is a downstream target gene of miR-490-3p. The protein levels of TMOD3, p-p38 and p-ERK were significantly downregulated in Huh-7 cells following transfection with miR-490-3p mimics, and the overexpression of TMOD3 attenuated these effects. In conclusion, the aforementioned results suggest that the overexpression of miR-490-3p inhibited the proliferation and invasion of HCC cells by targeting TMOD3. Therefore, the miR-490-3p/TMOD3 axis may be a potent target for the treatment of HCC.