LncRNA LINC00534 regulates cell proliferation and migration via the miR‐494‐3p/PTEN axis in HTR‐8/SVneo cells

BackgroundLncRNA LINC00534 has been found to be differentially expressed in placental tissue samples of preeclampsia (PE), but the exact mechanism is still unclear.MethodsIn vitro assays were carried out in HTR‐8/SVneo cells using various methods, including cell counting kit‐8 (CCK‐8), transwells, flow cytometry, and Western blotting (WB) and quantitative polymerase chain reaction. RNA pull‐down and bioinformatics analysis were applied to examine other potential underlying mechanisms involved.ResultsWe found that there was a high expression of LINC00534 in the placental tissues of patients with PE. LINC00534 overexpression (OE) significantly inhibited cell proliferation and migration as well as accelerated cell apoptosis in HTR8/SVneo cells. The knockdown of LINC00534 produced an opposite trend. Mechanistically, LINC00534 promoted the expressions of PTEN (Phosphatase and tensin homolog) through decreasing miR‐494‐3p. Further rescue studies showed that LINC00534 played a role by targeting mir‐494‐3p, which controlled the growth and migration of HTR‐8/SVneo trophoblast cells via regulating PTEN/PI3K/AKT (Phosphatidylinositol3‐kinase/protein kinase B). Moreover, lncRNA pull‐down assay identified 198 potential bound proteins for LINC00534. Those proteins were mostly involved in RNA processing and modification, posttranslational modification, protein turnover, and chaperones.ConclusionOverall, by suppressing HTR8/SVneo cell growth and migration via the miR‐494‐3p/PTEN axis and other mechanisms, LINC00534 offers new insight into PE pathogenesis.     

Silencing LINC00665 inhibits cutaneous melanoma in vitro progression and induces apoptosis via the miR‐339‐3p/TUBB

BackgroundLncRNAs are closely related to cutaneous melanoma (CM) tumorigenesis and metastasis, and it can affect the progression of CM by regulating cell proliferation, migration, invasion, apoptosis, and other cellular mechanisms. This study investigated the role of LINC00665 in CM.MethodsExpressions of LINC00665, miR‐339‐3p, and tubulin beta chain (TUBB) in CM cells were analyzed by qRT‐PCR and/or Western blot. The LINC00665/miR‐339‐3p/TUBB targeting network was predicted by bioinformatics tools, screened out by Venn diagrams and analyzed by Pearson''s correlation coefficients, followed by validation via dual‐luciferase reporter assay and/or pull‐down assay. Transfection of siLINC00665 or miR‐339‐3p inhibitor/mimic was conducted with CM cells whose viability, proliferation, migration, invasion, cell cycle progression, and apoptosis were measured by CCK‐8 assay, colony formation assay, wound healing assay, Transwell assay, and flow cytometry. The associations of TUBB with tumor biological characteristics and other proteins were analyzed by CanserSEA and String, respectively.ResultsHigh‐expressed LINC00665 was detected in CM cells. Silencing LINC00665 decreased CM cell viability; inhibited colony formation, cell cycle progression, migration and invasion; enhanced apoptosis; and upregulated miR‐339‐3p. LINC00665 targeted miR‐339‐3p which targeted TUBB. MiR‐339‐3p upregulation induced effects similar to the LINC00665‐silencing‐induced effects and could downregulate TUBB, which was associated with malignant behaviors and related to other five proteins. MiR‐339‐3p downregulation induced the opposite effects of what miR‐339‐3p upregulation induced, and the miR‐339‐3p downregulation‐induced effects could be reversed by LINC00665 silencing.ConclusionSilencing LINC00665 inhibits in vitro CM progression and induces apoptosis via the miR‐339‐3p/TUBB axis.     

Hsa_circ_0002082 up‐regulates Centromere Protein F via abolishing miR‐508‐3p to promote breast cancer progression

BackgroundCircular RNAs (circRNAs) dysregulation has been revealed to function in the pathological processes of cancers. Herein, the role and mechanisms of hsa_circ_0002082 in breast cancer (BC) progression were elucidated.MethodsIn vivo and in vitro functional experiments were conducted, and the interaction between miR‐508‐3p and hsa_circ_0002082 or Centromere Protein F (CENPF) was elucidated.ResultsHsa_circ_0002082 expression was higher in BC tissues and cell lines. Functionally, knockdown of hsa_circ_0002082 induced apoptosis and suppressed proliferation and metastasis in BC cells in vitro. Mechanistically, hsa_circ_0002082 targeted miR‐508‐3p, which was confirmed to be decreased in BC. MiR‐508‐3p overexpression suppressed BC cell malignant phenotypes, moreover, inhibition of miR‐508‐3p attenuated the anticancer action of hsa_circ_0002082 silencing on BC cells. Besides that, miR‐508‐3p targeted CENPF, CENPF was highly expressed in BC, CENPF up‐regulation reversed the suppressive impacts of miR‐508‐3p on BC cell growth and metastasis. Besides, hsa_circ_0002082 silencing impeded BC growth in nude mice.ConclusionKnockdown of hsa_circ_0002082 suppresses breast cancer growth and metastasis by miR‐508‐3p/CENPF axis, suggesting that hsa_circ_0002082 may be a promising target for breast cancer treatment.     

Decrease in LINC00963 attenuates the progression of pulmonary arterial hypertension via microRNA‐328‐3p/profilin 1 axis

BackgroundPulmonary arterial hypertension (PAH) is a severe cardiopulmonary disease characterized by vascular hyperplasia and remodeling. Long noncoding RNA LINC00963 can regulate cell proliferation and metastasis in nonsmall cell lung cancer. However, the function of LINC00963 on PAH progression is rarely reported.MethodsQuantitative real‐time PCR was used to determine the expression levels of LINC00963, microRNA (miRNA)‐328‐3p, and profilin 1 (PFN1), as well as vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF‐2), and hypoxia‐inducible factor (HIF)‐α. The protein level of PFN1 was measured by western blotting. The viability and migration of hypoxia‐induced pulmonary arterial smooth muscle cells (PASMCs) were assessed by 3‐(4, 5‐dimethyl‐2‐thiazolyl)‐2, 5‐diphenyl‐2‐h‐tetrazolium bromide, and transwell assays, respectively. The target relationships between miR‐328‐3p and LINC00963/PFN1 were confirmed by dual‐luciferase reporter assay. A PAH mouse model was conducted to explore the effects of hypoxia on cardiopulmonary functions.ResultsIn hypoxia‐induced PASMCs and PAH mouse model, high expression levels of LINC00963 and PFN1, and low expression of miR‐328‐3p, were determined. The viability, migration of hypoxia‐induced PASMCs, the expression of VEGF, FGF‐2, and HIF‐α were significantly repressed by transfection of si‐LINC00963 or miR‐328‐3p mimics. The inhibitory effects of LINC00963 silencing on cell viability, migration, and the levels of VEGF, FGF‐2, and HIF‐α were partly eliminated by miR‐328‐3p inhibitor or increasing the expression of PFN1. Hypoxia treatment increased the levels of RVSP, mPAP, and RV/(LV+S), as well as the thickness of pulmonary artery wall.ConclusionsSilencing of LINC00963 ameliorates PAH via modulating miR‐328‐3p/PFN1.     

Circular RNA circβ‐catenin aggravates the malignant phenotype of non‐small‐cell lung cancer via encoding a peptide

BackgroundMore and more evidences demonstrate that circular RNAs (circNRAs) can encode protein. As a circRNA with translation capabilities, outcomes of circβ‐catenin in non‐small cell lung cancer (NSCLC) still need to be explored.MethodThe research methods of circβ‐catenin in the article include qRT‐PCR, wound healing assay, CCK‐8, colony formation, and Transwell assay. Western blotting and immunofluorescence were provided to detect protein expression levels and peptide encoded by circβ‐catenin, respectively.ResultsA prominently higher circβ‐catenin expression was found in NSCLC tissues. Silencing of circβ‐catenin was able to inhibit NSCLC cell migrating, invasive, and proliferative phenotypes. Overexpression of circβ‐catenin could enhance the migrating, invasive, and proliferative phenotypes of NSCLC cells. Importantly, circβ‐catenin was found to encode a peptide in NSCLC cells. Silencing or overexpression of circβ‐catenin could reduce or increase β‐catenin protein expression via suppressing the degradation of β‐catenin.ConclusionCircβ‐catenin could promote NSCLC cell malignant phenotypes via peptide‐regulated β‐catenin pathway. Our study provided a new understanding for the mechanisms of NSCLC.     

Circular RNA hsa_circ_0011298 enhances Taxol resistance of non‐small cell lung cancer by regulating miR‐486‐3p/CRABP2 axis

BackgroundCircular RNAs (circRNAs) serve as critical regulators in the chemoresistance of human cancers, including non‐small cell lung cancer (NSCLC). We aimed to explore the role of hsa_circ_0011298 (circ_0011298) and its mechanism in Taxol resistance of NSCLC.MethodsCirc_0011298, microRNA‐486‐3p (miR‐486‐3p), and CRABP2 mRNA expression were determined using qRT‐PCR. EdU and MTT assays were used to detect cell proliferation. Cell cycle distribution and cell apoptosis were detected by flow cytometry. Cell migratory and invasive abilities were detected using transwell assay. Cellular glycolysis was determined by specific kits. Protein levels were examined by western blot. Dual‐luciferase reporter and RIP assays were performed to confirm the relationship between miR‐486‐3p and circ_0011298 or CRABP2. Xenograft mice model was established to confirm the function of circ_0011298 in vivo.ResultsCirc_0011298 was overexpressed in Taxol‐resistant NSCLC cells and tissues. Circ_0011298 knockdown enhanced Taxol sensitivity by decreasing cell proliferation, migration, invasion, and glycolysis and inducing apoptosis and cell cycle arrest in Taxol‐resistant NSCLC cells. Circ_0011298 was a sponge of miR‐486‐3p, and the impact of circ_0011298 silencing on Taxol resistance was rescued by miR‐486‐3p inhibition. Moreover, miR‐486‐3p directly targeted CRABP2, and miR‐486‐3p inhibited Taxol resistance by targeting CRABP2. Furthermore, circ_0011298 regulated CRABP2 expression through targeting miR‐486‐3p. Importantly, circ_0011298 interference elevated Taxol sensitivity of NSCLC in vivo.ConclusionCirc_0011298 elevated Taxol resistance of NSCLC by sponging miR‐486‐3p and upregulating CRABP2, providing a possible circRNA‐targeted therapy for NSCLC.     

Hsa_circ_0005529 promotes ZEB1 expression by regulating miR‐873‐5p and enhancing proliferation,invasion, and migration in gastric cancer cell lines

BackgroundGastric cancer is a relatively common tumor. As circular RNAs (circRNAs) are documented to modulate proliferation and metastasis in various cancers, we evaluated the functions of circRNAs, in particular, hsa_circ_0005529, in gastric cancer cells.MethodsLevels of hsa_circ_0005529 and miR‐873‐5p were examined by qRT‐PCR, and the presence of hsa_circ_0005529 was confirmed by RNase R treatment. CCK‐8, wound‐healing, and Transwell assays were used to assess proliferation, migration, and invasion, respectively, while Western blotting was used to determine levels of zinc finger E‐box‐binding homeobox 1 (ZEB1) and dual‐luciferase reporter assays to examine relationships between hsa_circ_0005529 and miR‐873‐5p.Resultshsa_circ_0005529 was strongly expressed in gastric cancer where it stimulated tumorigenic behavior. Furthermore, hsa_circ_0005529 was shown to promote ZEB1 expression by sponging miR‐873‐5p, an inhibitor of ZEB1 expression.ConclusionOur research showed that hsa_circ_0005529 promoted tumorigenic behavior in gastric cancer cells by adsorbing miR‐873‐5p to modulate ZEB1 levels. This suggests that hsa_circ_0005529 may be useful as a biomarker and target for diagnosing and treating gastric cancer.     

CircRNA WHSC1 promotes non‐small cell lung cancer progression via sponging microRNA‐296‐3p and up‐regulating expression of AKT serine/threonine kinase 3

BackgroundLung cancer is the most commonly diagnosed cancer and leading cause of cancer death, with 80%–85% of non‐small cell lung cancer (NSCLC). Circular RNAs (circRNAs) have been shown to be promising early diagnostic and therapeutic molecular biomarkers for NSCLC. However, biological role and regulatory mechanism of circRNA WHSC1 (circWHSC1) in NSCLC are unknown. Therefore, we aim to explore the function and mechanism of circWHSC1 in NSCLC oncogenesis and progression.MethodsqRT‐PCR was used for circWHSC1 level evaluation; Kaplan‐Meier was used for survival analysis; bioinformatics, dual‐luciferase activity, and RNA pull‐down were used for evaluating competing endogenous RNA (ceRNA) network; cell viability, colony formation, apoptosis, migration, and invasion were used for cell function analysis; function gain and loss with rescue experiments were used for exploring mechanism of circWHSC1 in NSCLC development.ResultsSignificantly up‐regulated circWHSC1 and down‐regulated microRNA‐296‐3p (miR‐296‐3p) were identified in NSCLC tissues and cells. Up‐regulated circWHSC1 was associated with poor prognosis in NSCLC patients. MiR‐296‐3p was sponged by circWHSC1, and AKT serine/threonine kinase 3 (AKT3) was target of miR‐296‐3p; meanwhile, miR‐296‐3p over‐expression significantly down‐regulated AKT3 expression, and co‐transfecting anti‐miR‐296‐3p rescued circWHSC1 silence caused AKT3 down‐regulation. CircWHSC1 silence significantly inhibited colony formation, viability, invasion, and migration, while increased NSCLC cell apoptosis, which were partially rescued by anti‐miR‐296‐3p.ConclusionCircWHSC1 is an independent indicator of poor prognosis in NSCLC patients, and functions as a ceRNA of miR‐296‐3p to up‐regulate AKT3, consequently promotes NSCLC cell growth and metastasis. Targeting circWHSC1 might be a prospective strategy for diagnosis, therapeutics, and prognosis of NSCLC.     

Hsa_circ_0092887 targeting miR‐490‐5p/UBE2T promotes paclitaxel resistance in non‐small cell lung cancer

BackgroundChemoresistance is a major contributing factor to cancer treatment failure. Emerging research reveals that circular RNA (circRNA) dysregulation is implicated in chemoresistance. Our current study aimed to investigate the involvement of hsa_circ_0092887 in paclitaxel (PTX) resistance in non‐small cell lung cancer (NSCLC).MethodsRT‐qPCR as well as western blotting were used for the analysis of hsa_circ_0092887, miR‐490‐5p and UBE2T expression in PTX‐resistant NSCLC tumor tissues and cells. CCK‐8 assay was done to determine the IC50 value of PTX. CCK‐8 assay, wound healing assay, analysis of apoptosis related proteins (Bax and Bcl‐2), and xenograft mouse models were utilized to investigate the role of hsa_circ_0092887 in PTX‐resistance in NSCLC. The binding sites of miR‐490‐5p to hsa_circ_0092887 or UBE2T were predicted by bioinformatics tools and were verified by RIP and dual‐luciferase assays.ResultsExpression of hsa_Circ_0092887 was upregulated in NSCLC tumor samples/cell lines, and its expression was also higher in PTX‐resistant tumor samples/cell lines when compared with their respective controls. Silencing of hsa_circ_0092887 in PTX‐treated NSCLC cells inhibited cell proliferation and migration, induced apoptosis, and suppressed tumor growth in xenograft mouse models in vivo. MiR‐490‐5p was a direct target of hsa_circ_0092887, and UBE2T was a functional downstream target of hsa_circ_0092887/miR‐490‐5p axis. Hsa_circ_0092887 depletion‐induced anti‐cancer effects in PTX‐treated NSCLC cells were reversed by miR‐490‐5p inhibitor. Furthermore, inhibition of miR‐490‐5p strengthened UBE2T expression, thereby attenuating the anti‐cancer effects caused by UBE2T knockdown.ConclusionHsa_circ_0092887 depletion alleviated PTX‐resistance in NSCLC cells via modulating the miR‐490‐5p/UBE2T axis, and the targeted management of hsa_circ_0092887‐mediated signaling axis might contribute to PTX‐resistance intervention in NSCLC.     

Hsa_circ_0058129 regulates papillary thyroid cancer development via miR‐873‐5p/follistatin‐like 1 axis

BackgroundPapillary thyroid cancer (PTC) is an endocrine malignancy with a high incidence. Circular RNAs (circRNAs) participate in regulating PTC. Here, we analyzed the role of hsa_circ_0058129 (circ_0058129) in PTC.MethodsThe expression of circ_0058129, fibronectin 1 (FN1) mRNA, microRNA‐873‐5p (miR‐873‐5p), and follistatin‐like 1 (FSTL1) was detected by qRT‐PCR and western blot. Cell proliferation was analyzed by CCK‐8, EdU, and flow cytometry analysis assays. Cell migration and invasion were evaluated by Transwell assay. The targeting relationship of miR‐873‐5p and circ_0058129 or FSTL1 was identified through dual‐luciferase reporter assay, RIP assay, and RNA pull‐down assay. Xenograft mouse model assay was implemented to determine the effect of circ_0058129 on tumor formation in vivo.ResultsThe circ_0058129 and FSTL1 abundances were increased, while the miR‐873‐5p content was decreased in PTC tissues and cells compared with control groups. Circ_0058129 shortage inhibited PTC cell proliferation, migration, and invasion. Moreover, miR‐873‐5p repressed PTC cell malignancy by binding to FSTL1. Circ_0058129 targeted miR‐873‐5p to regulate FSTL1.ConclusionCirc_0058129 expedited PTC progression through the miR‐873‐5p/FSTL1 pathway.     

Hsa_circ_0050102 regulates the pancreatic cancer development via miR‐218‐5p/PPME1 axis

BackgroundPancreatic cancer (PC) is a malignancy worldwide. Circular RNAs (circRNAs) affects the growth of PC, nonetheless the mechanism is blurry. Here, we reconnoitered the parts of hsa_circ_0050102 in PC.MethodsHsa_circ_0050102, microRNA‐218‐5p (miR‐218‐5p) and protein phosphatase methylesterase 1 (PPME1) abundances were indicated by quantitative RT‐PCR or Western blot. Moreover, the cell functions were uncovered. Additionally, the relation of miR‐218‐5p and hsa_circ_0050102 or PPME1 was identified by dual‐luciferase reporter assay. Ultimately, the mice teats were utilized to quantity the part of hsa_circ_0050102.ResultsHsa_circ_0050102 and PPME1 contents were increased, and the miR‐218‐5p was dwindled in PC. Hsa_circ_0050102 lack subdued cell vitality, colony formation, cell migration and invasion, and angiogenesis, but endorsed cell apoptosis in PC cells. Furthermore, miR‐218‐5p was established to block the development of PC cells via PPME1. Hsa_circ_0050102 bound to miR‐218‐5p to adjust the content of PPME1.ConclusionHsa_circ_0050102 expedited the expansion of PC through growing PPME1 abundance by adjusting miR‐218‐5p.     

MiR‐221‐3p and miR‐92a‐3p enhances smoking‐induced inflammation in COPD

BackgroundSmoking is likely to facilitate airway inflammation and finally contributes to chronic obstructive pulmonary disease (COPD). This investigation was intended to elucidate miRNAs that were involved in smoking‐induced COPD.MethodsAltogether 155 COPD patients and 77 healthy volunteers were recruited, and their serum levels of miR‐221‐3p and miR‐92a‐3p were determined. Besides, human bronchial epithelial cells (16HBECs) were purchased, and they were treated by varying concentrations of cigarette smoke extract (CSE). The 16HBECs were, additionally, transfected by miR‐221‐3p mimic, miR‐92a‐3p mimic, miR‐221‐3p inhibitor or miR‐92a‐3p inhibitor, and cytokines released by them, including TNF‐α, IL‐8, IL‐1β, and TGF‐β1, were monitored using enzyme linked immunosorbent assay (ELISA) kits.ResultsChronic obstructive pulmonary disease patients possessed higher serum levels of miR‐221‐3p and miR‐92a‐3p than healthy volunteers (p < 0.05), and both miR‐221‐3p and miR‐92a‐3p were effective biomarkers in diagnosing stable COPD from acute exacerbation COPD. Moreover, viability of 16HBECs was undermined by CSE treatment (p < 0.05), and exposure to CSE facilitated 16HBECs’ release of TNF‐α, IL‐8, IL‐1β, and TGF‐β1 (p < 0.05). Furthermore, miR‐221‐3p/miR‐92a‐3p expression in 16HBECs was significantly suppressed after transfection of miR‐221‐3p/miR‐92a‐3p inhibitor (p < 0.05), which abated CSE‐triggered increase in cytokine production and decline in viability of 16HBECs (p < 0.05).ConclusionMiR‐221‐3p and miR‐92a‐3p were involved in CSE‐induced hyperinflammation of COPD, suggesting that they were favorable alternatives in diagnosing COPD patients with smoking history.     

hsa_circ_0000285 facilitates thyroid cancer progression by regulating miR‐127‐5p/CDH2

Thyroid cancer (THCA) is a leading endocrine cancer and becomes the fifth most commonly diagnosed malignancy in females. It is confirmed that circular RNAs (circRNAs) perform regulatory potencies in the pathological progress of THCA. Our purpose was to certify the trait of hsa_circ_0000285 (circ_0000285) and investigate its modulatory mechanism in THCA progression. We identified the expression profile of hsa_circ_0000285 in THCA by conducting qRT‐PCR assay. Therewith, the potential of hsa_circ_0000285 in THCA development was determined with a set of functional experiments, including CCK‐8, wound healing assay, Western blot, and xenograft model. The molecular mechanism underlying hsa_circ_0000285 was investigated with bioinformatic analysis, RIP and dual‐luciferase reporter experiments. As opposed to normal samples and cells, hsa_circ_0000285 level was overtly increased in THCA specimens and cells. The downregulation of hsa_circ_0000285 weakened the proliferative and migratory capacity of THCA cells and promoted cell apoptosis. In addition, hsa_circ_0000285 silence suppressed the tumor growth of xenograft model mice in vivo. Notably, we demonstrated that hsa_circ_0000285 might target miR‐127‐5p/CDH2 axis in THCA. Afterward, our findings manifested that miR‐127‐5p attenuation blocked the function of hsa_circ_0000285 depletion in THCA cells. In the final step, CDH2 was proven to mediate the repressive potency of miR‐127‐5p in the malignant behaviors of THCA. Mechanistically, hsa_circ_0000285 induced the development of THCA via functioning as a competing endogenous RNA (ceRNA) of miR‐127‐5p to enhance CDH2 expression, which provided a new perspective for THCA therapy.     

Hsa_circ_0045932 regulates the progression of colorectal cancer by regulating HK2 through sponging miR‐873‐5p

BackgroundCircular RNAs (circRNAs) have been confirmed to be key regulators for colorectal cancer (CRC) progression. The purpose of this research was to explore the biological role and mechanism of hsa_circ_0045932 in CRC.MethodsRT‐qPCR and Western blot (WB) were applied to examine RNA and protein levels, respectively. MTT assay, EdU assay, and transwell assay were used to detect cell proliferative, migration, and invasion. Glucose uptake and lactic acid level were determined to assess cellular glycolysis. Dual‐luciferase reporter and RIP assays were carried out to detect the relationship between miR‐873‐5p and hsa_circ_0045932 or hexokinase 2 (HK2). Xenograft mice model was established to confirm the function of hsa_circ_0045932 in vivo.ResultsHsa_circ_0045932 was overexpressed in CRC tissue samples and cells. Hsa_circ_0045932 knockdown repressed CRC cell proliferation, invasion, migration, and glycolysis abilities in vitro. MiR‐873‐5p could be sponged by hsa_circ_0045932, and its inhibitor also reversed the inhibitory effect of hsa_circ_0045932 knockdown on CRC cell progression. HK2 was targeted by miR‐873‐5p, and hsa_circ_0045932 regulated HK2 expression through targeting miR‐873‐5p. Overexpression of HK2 reversed the repressive effect of hsa_circ_0045932 knockdown on CRC cell malignant behaviors. Furthermore, the pro‐tumor role of hsa_circ_0045932 in vivo was also confirmed using animal experiments.ConclusionHsa_circ_0045932 promoted CRC progression through sponging miR‐873‐5p to up‐regulate HK2, which might offer novel therapeutic target for CRC clinical intervention.     

Downregulation of Talin‐1 is associated with the increased expression of miR‐182‐5p and miR‐9‐5p in coronary artery disease

BackgroundEvidence indicates that the dysregulation of extracellular matrix (ECM) components can lead to cardiovascular diseases. The Talin‐1 (TLN1) gene is a major component of the ECM, and it mediates integrin adhesion to the ECM. In this study, we aimed to determine microRNAs (miRs) that regulate the expression of TLN1 and determine expression alterations in TLN1 and its targeting miRs in coronary artery disease (CAD).MethodsData sets of CAD and normal samples of blood exosomes were downloaded, and TLN1 was chosen as one of the genes with differential expressions in an in silico analysis. Next, miR‐182‐5p and miR‐9‐5p, which have a binding site on 3´‐UTR of TLN1, were selected using bioinformatics tools. Then, the miR target site was cloned in the psiCHECK‐2 vector, and direct interaction between the miR target site and the TLN1 3′‐UTR putative target site was investigated by luciferase assay. The expression of miR‐182‐5p, miR‐9‐5p, and TLN1 in the serum samples of CAD and non‐CAD individuals was assessed via a real‐time quantitative polymerase chain reaction.ResultsOur data revealed that miR‐182‐5p directly regulated the expression of TLN1. Moreover, miR‐182‐5p and miR‐9‐5p were significantly upregulated in the CAD group. Hence, both bioinformatics and experimental analyses determined the downregulated expression of TLN1 in the CAD samples.ConclusionsOur findings demonstrated that miR‐182‐5p and miR‐9‐5p could play significant roles in TLN1 regulation and participate in CAD development by targeting TLN1. These findings introduce novel biomarkers with a potential role in CAD pathogenesis.     

LncRNA FGF14‐AS2 represses growth of prostate carcinoma cells via modulating miR‐96‐5p/AJAP1 axis

ObjectiveThis investigation devoted to lncRNA FGF14 antisense RNA 2 (FGF14‐AS2) in prostate carcinoma progression.MethodsThe levels of lncRNA FGF14‐AS2, miR‐96‐5p, and Adherens junction‐associated protein‐1 (AJAP1) in prostate carcinoma were tested by Western blot and qRT‐PCR. How these two genes interacted was confirmed by RNA immunoprecipitation and dualluciferase gene methods. The effect of FGF14‐AS2/miR‐96‐5p/AJAP1 axis in prostate carcinoma progression was determined by MTT, Transwell, and nude mice tumor model.ResultsFGF14‐AS2 was a downregulated lncRNA in prostate carcinoma tissue and cells. FGF14‐AS2 could restrain miR‐96‐5p expression while miR‐96‐5p hampered AJAP1. FGF14‐AS2 could effectively decrease the biological behaviors of prostate carcinoma cells, while knock‐down of FGF14‐AS2 triggered opposite results. Moreover, miR‐96‐5p mimic presented a cancer promoter role in prostate carcinoma cells. AJAP1 expression level could affect levels of proteins related to epithelial‐mesenchymal transition. In vivo experiment suggested that overexpressing FGF14‐AS2 could reverse the promotion of silenced AJAP1 on prostate carcinoma cell metastasis, thus to inhibit tumor growth.ConclusionlncRNA FGF14‐AS2 was a downregulated lncRNA in prostate carcinoma and influenced cell proliferation and metastasis. The influence relied on modulating miR‐96‐5p and its target gene AJAP1.     

miR‐125a‐5p promotes gastric cancer growth and invasion by regulating the Hippo pathway

ObjectiveThis study was carried out to explore the potential involvement of miR‐125a‐5p in the oncogenic effects of EphA2, TAZ, and TEAD2 and the activity of the Hippo signaling pathway in gastric cancer progression.MethodsIn vitro transfection of miR‐125a‐5p mimics or inhibitors, qRT‐PCR, colony formation assays, and cell invasion assays were used to assess the effect of miR‐125a‐5p on the growth and invasion in gastric cancer (GC). Male nude mice bearing tumors derived from human GC cells were used for evaluating the effects of miR‐125a‐5p on tumor growth. Luciferase reporter assay, immunofluorescence, immunohistochemistry, qRT‐PCR, and immunoblotting were performed to explore the role of miR‐125a‐5p in the epithelial‐mesenchymal transition (EMT) and association among miR‐125a‐5p, EphA2, TAZ, and TEAD2 in GC cells.ResultsMiR‐125a‐5p enhanced GC cell viability and invasion in vitro, whereas inhibition of miR‐125a‐5p using a specific inhibitor and antagomir suppressed cancer cell invasion and tumor growth. Moreover, inhibition of miR‐125a‐5p reversed EMT in vitro. miR‐125a‐5p upregulated the expression of EphA2, TAZ, and TEAD2, promoted TAZ nuclear translocation, and induced changes in the activity of the Hippo pathway by enhancing the expression of TAZ target genes. Finally, miR‐125a‐5p was overexpressed in late‐stage GCs, and positive correlations were observed with its targets EphA2, TAZ, and TEAD2.ConclusionmiR‐125a‐5p can promote GC growth and invasion by upregulating the expression of EphA2, TAZ, and TEAD2.