MiR-431 promotes cardiomyocyte proliferation by targeting FBXO32 expression.

BACKGROUND: The induction of cardiomyocyte (CM) proliferation is a promising approach for cardiac regeneration following myocardial injury. MicroRNAs (miRNAs) have been reported to regulate CM proliferation. In particular, miR-431 expression decreases during cardiac development, according to Gene Expression Omnibus (GEO) microarray data. However, whether miR-431 regulates CM proliferation has not been thoroughly investigated. METHODS: We used integrated bioinformatics analysis of GEO datasets to identify the most significantly differentially expressed miRNAs. Real-time quantitative PCR and fluorescence in situ hybridization were performed to determine the miRNA expression patterns in hearts. Gain- and loss-of-function assays were conducted to detect the role of miRNA in CM proliferation. Additionally, we detected whether miR-431 affected CM proliferation in a myocardial infarction model. The TargetScan, miRDB and miRWalk online databases were used to predict the potential target genes of miRNAs. Luciferase reporter assays were used to study miRNA interactions with the targeting mRNA. RESULTS: First, we found a significant reduction in miR-431 levels during cardiac development. Then, by overexpression and inhibition of miR-431, we demonstrated that miR-431 promotes CM proliferation in vitro and in vivo, as determined by immunofluorescence assays of 5-ethynyl-2'-deoxyuridine (EdU), pH3, Aurora B and CM count, whereas miR-431 inhibition suppresses CM proliferation. Then, we found that miR-431 improved cardiac function post-myocardial infarction. In addition, we identified FBXO32 as a direct target gene of miR-431, with FBXO32 mRNA and protein expression being suppressed by miR-431. FBXO32 inhibited CM proliferation. Overexpression of FBXO32 blocks the enhanced effect of miR-431 on CM proliferation, suggesting that FBXO32 is a functional target of miR-431 during CM proliferation. CONCLUSION: In summary, miR-431 promotes CM proliferation by targeting FBXO32, providing a potential molecular target for preventing myocardial injury.

MicroRNA-431-5p inhibits angiogenesis, lymphangiogenesis, and lymph node metastasis by affecting TGF-ß1/SMAD2/3 signaling via ZEB1 in gastric cancer.

Accumulating evidence suggests that lymphangiogenesis plays a crucial role in lymphatic metastasis, leading to tumor immune tolerance. However, the specific mechanism remains unclear. In this study, miR-431-5p was markedly downregulated in both gastric cancer (GC) tissues and plasma exosomes, and its expression were correlated negatively with LN metastasis and poor prognosis. Mechanistically, miR-431-5p weakens the TGF-ß1/SMAD2/3 signaling pathway by targeting ZEB1, thereby suppressing the secretion of VEGF-A and ANG2, which in turn hinders angiogenesis, lymphangiogenesis, and lymph node (LN) metastasis in GC. Experiments using a popliteal LN metastasis model in BALB/c nude mice demonstrated that miR-431-5p significantly reduced popliteal LN metastasis. Additionally, miR-431-5p enhances the efficacy of anti-PD1 treatment, particularly when combined with galunisertib, anti-PD1 treatment showing a synergistic effect in inhibiting GC progression in C57BL/6 mice. Collectively, these findings suggest that miR-431-5p may modulate the TGF-ß1/SMAD2/3 pathways by targeting ZEB1 to impede GC progression, angiogenesis, and lymphangiogenesis, making it a promising therapeutic target for GC management.

CircADSS contributes to hepatocellular carcinoma development by regulating miR-431-5p/TOP2A.

CircRNAs participated in regulating hepatocellular carcinoma (HCC), and the regulation function of circRNA adenylosuccinate synthase (circADSS) on HCC development is not clear. RT-qPCR and western blot were performed to detect RNA expression. Cell proliferation was analysed by CCK-8 and EdU assay. Cell cycle distribution was analysed by flow cytometry assay. Cell migration and invasion were measured by transwell assay. Mechanism assays were employed to examine the interaction between miR-431-5p and circADSS, or TOP2A. Xenograft mouse model was constructed for in vivo assay. CircADSS and TOP2A expression were boosted, while miR-431-5p was limited in tumour tissues and cells. CircADSS silencing decreased HCC cell proliferation, cell cycle progression, migration, invasion, as well as EMT. MiR-431-5p inhibitors or ectopic TOP2A expression could restore the effect of circADSS knockdown on HCC progression. There was target relationship between miR-431-5p and circADSS, or TOP2A. Knockdown of circADSS suppressed tumour growth in vivo. CircADSS could regulate HCC cell malignancy by miR-431-5p/TOP2A axis.

CircRNA circSTIL inhibits ferroptosis in colorectal cancer via miR-431/SLC7A11 axis.

Ferroptosis is an emerging programmed cell death and plays essential roles in tumorigenesis, including colorectal cancer (CRC). The present study intended to disclose the role of a novel oncogene circular RNA (circRNA) circSTIL in CRC phenotypes, especially ferroptosis. The expression of circSTIL was measured in CRC tissues and cells. Then, the impacts of circSTIL expression on the proliferation and ferroptosis of CRC cells were examined by loss-of-function assays in vitro. Bioinformatics, luciferase reporter assay and cell rescue assay were further performed to reveal the ceRNA-associated mechanism of circSTIL. CircSTIL was significantly upregulated in CRC. Cell proliferation was suppressed while ferroptosis was induced with the silencing of circSTIL in CRC cells. Interestingly, circSTIL competed with miR-431 for solute carrier family 7 member 11 (SLC7A11) binding. Additionally, miR-431 suppression or SLC7A11 overexpression overturned circSTIL silencing-mediated cell phenotypes in CRC cells. CircSTIL promotes CRC cell proliferation and suppresses ferroptosis in vitro via miR-431/SLC7A11 signaling, revealing the pathogenesis of CRC, and providing potential therapeutic targets of CRC.

miR-431 promotes differentiation and regeneration of old skeletal muscle by targeting Smad4.

The myogenic capacity of myoblasts decreases in skeletal muscle with age. In addition to environmental factors, intrinsic factors are important for maintaining the regenerative potential of muscle progenitor cells, but their identities are largely unknown. Here, comparative analysis of microRNA (miRNA) expression profiles in young and old myoblasts uncovered miR-431 as a novel miRNA showing markedly reduced abundance in aged myoblasts. Importantly, elevating miR-431 improved the myogenic capacity of old myoblasts, while inhibiting endogenous miR-431 lowered myogenesis. Bioinformatic and biochemical analyses revealed that miR-431 directly interacted with the 3' untranslated region (UTR) of Smad4 mRNA, which encodes one of the downstream effectors of TGF-ß signaling. In keeping with the low levels of miR-431 in old myoblasts, SMAD4 levels increased in this myoblast population. Interestingly, in an in vivo model of muscle regeneration following cardiotoxin injury, ectopic miR-431 injection greatly improved muscle regeneration and reduced SMAD4 levels. Consistent with the finding that the mouse miR-431 seed sequence in the Smad4 3' UTR is conserved in the human SMAD4 3' UTR, inhibition of miR-431 also repressed the myogenic capacity of human skeletal myoblasts. Taken together, our results suggest that the age-associated miR-431 plays a key role in maintaining the myogenic ability of skeletal muscle with age.

Circular RNA circCSPP1 promotes the occurrence and development of colon cancer by sponging miR-431 and regulating ROCK1 and ZEB1.

BACKGROUND: Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study aims to investigate the role of a novel circular RNA (circCSPP1) in colon cancer and its underlying molecular mechanisms. METHODS: Bioinformatics analysis and reverse transcription-quantitative PCR were used to detect the expression levels of circCSPP1 in colon cancer tissues and cell lines. The effects of circCSPP1 on the behavior of colon cancer cells were investigated using CCK-8, transwell and clonogenic assays. Bioinformatics analysis along with luciferase, fluorescence in situ hybridization and RNA pull-down assays were used to reveal the interaction between circCSPP1, microRNA (miR)-431, Rho associated coiled-coil containing protein kinase 1 (ROCK1) and zinc finger E-box binding homeobox 1 (ZEB1). RESULTS: It was found that circCSPP1 expression was significantly upregulated in colon cancer tissues and cell lines. Overexpression of circCSPP1 significantly promoted the proliferation, migration and invasion of colon cancer cells, whereas silencing of circCSPP1 exerted opposite effects. Mechanistically, circCSPP1 was found to bind with miR-431. In addition, ROCK1 and ZEB1 were identified as the target genes of miR-431. Rescue experiments further confirmed the interaction between circCSPP1, miR-431, ROCK1 and ZEB1. Moreover, circCSPP1 promoted the expression level of ROCK1, cyclin D1, cyclin-dependent kinase 4, ZEB1 and Snail, and lowered the E-cadherin expression level. CONCLUSION: Taken together, the findings of the present study indicated that circCSPP1 may function as a competing endogenous RNA in the progression of colon cancer by regulating the miR-431/ROCK1 and miR-431/ZEB1 signaling axes.

Circ_0078710 promotes the development of liver cancer by upregulating TXNDC5 via miR-431-5p.

INTRODUCTION AND OBJECTIVES: Liver cancer, with high recurrence and metastasis rate, is a common malignant tumor. Circular RNA_0078710 (circ_0078710) has been shown to be take part in the advance of hepatocellular carcinoma. However, the interaction between circ_0091579 and microRNA-431-5p (miR-431-5p) in liver cancer has not been studied. MATERIALS AND METHODS: The expressions of circ_0078710, miR-431-5p and Thioredoxin domain-containing 5 (TXNDC5) in liver cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The effect of cric_0078710 in liver cancer cells was assessed by Cell Counting Kit-8 (CCK-8) assay, Transwell, flow cytometry and Dual-luciferase reporter assay. Glycolysis metabolism was examined by lactate production, glucose uptake and ATP level. The protein levels of ki-67, bax and TXNEC5 were tested by western blot. The role of circ_0078710 in vivo was determined by animal study. RESULTS: Circ_0078710 and TXNDC5 were notably expressed in liver cancer tissues and cells. Circ_0078710 knockdown diminished proliferation, migration, invasion and glycolytic metabolism of huh7 and Hep3B cells, and accelerated cell apoptosis. MiR-431-5p is the target of circ_0078710, and silence circ_0078710 can inhibit the malignant behavior and glycolysis of hepatocellular carcinoma (HCC) cells by releasing miR-431-5p. In addition, TXNDC5 was a target of miR-431-5p, and overexpression of TXNDC5 restored cell proliferation and glycolysis inhibition due to miR-431-5p. Animal experiments made clear the anti-tumor effect of circ_0078710 knockdown. CONCLUSION: Circ_0078710 promotes the progression of liver cancer by regulating TXNDC5 expression by targeting miR-431-5p. These results demonstrate that circ_0078710 could be a remedy target for liver cancer.

CircADAMTS6/miR-431-5p axis regulate interleukin-1ß induced chondrocyte apoptosis.

BACKGROUND: Growing evidence suggests that circular RNAs (circRNAs) are involved in the development of osteoarthritis (OA). The present study aimed to explore the CircADAMTS6/miR-431-5p axis with respect to regulating interleukin-1ß (IL-1ß) induced chondrocyte apoptosis. METHODS: We first evaluated the differentially expressed circRNAs between normal chondrocytes and interleukin (IL)-1ß-stimulated chondrocytes. Then, bioinformatic analysis was performed to identify the role and function of circADAMTS6. Small interfering RNA-expressing or overexpressing circADAMTS6 lentiviral vectors were used for transduction of chondrocytes. Annexin-V-fluorescein isothiocyanate (FITC) double staining was performed to measure the apoptotic rate of the chondrocytes in each group. Finally, a dual luciferase reporter assay was performed to identify the target relationship between circADAMTS6 and miR-431-5p. RESULTS: After treatment with IL-1ß, circADAMTS6 was down-regulated compared to the normal chondrocyte group. The overexpression of circADAMTS6 inhibited apoptosis in human chondrocytes, as indicated by annexin-V-FITC double staining. However, overexpression of miR-431-5p had the opposite effect. A dual luciferase reporter assay indicated that circADAMTS6 could directly binding with miR-431-5p. CONCLUSIONS: Our findings demonstrate that the circADAMTS6/miR-431-5p axis comprises a new target for OA. Bioinformatic analysis suggested that circADAMTS6 acted as a sponge of miR-431-5p.

Overexpression of miR-431 attenuates hypoxia/reoxygenation-induced myocardial damage via autophagy-related 3.

Myocardial injury is still a serious condition damaging the public health. Clinically, myocardial injury often leads to cardiac dysfunction and, in severe cases, death. Reperfusion of the ischemic myocardial tissues can minimize acute myocardial infarction (AMI)-induced damage. MicroRNAs are commonly recognized in diverse diseases and are often involved in the development of myocardial ischemia/reperfusion injury. However, the role of miR-431 remains unclear in myocardial injury. In this study, we investigated the underlying mechanisms of miR-431 in the cell apoptosis and autophagy of human cardiomyocytes in hypoxia/reoxygenation (H/R). H/R treatment reduced cell viability, promoted cell apoptotic rate, and down-regulated the expression of miR-431 in human cardiomyocytes. The down-regulation of miR-431 by its inhibitor reduced cell viability and induced cell apoptosis in the human cardiomyocytes. Moreover, miR-431 down-regulated the expression of autophagy-related 3 (ATG3) via targeting the 3'-untranslated region of ATG3. Up-regulated expression of ATG3 by pcDNA3.1-ATG3 reversed the protective role of the overexpression of miR-431 on cell viability and cell apoptosis in H/R-treated human cardiomyocytes. More importantly, H/R treatments promoted autophagy in the human cardiomyocytes, and this effect was greatly alleviated via miR-431-mimic transfection. Our results suggested that miR-431 overexpression attenuated the H/R-induced myocardial damage at least partly through regulating the expression of ATG3.

miR-431 regulates granulosa cell function through the IRS2/PI3K/AKT signaling pathway.

MicroRNAs (miRNAs) regulate the functions of granulosa cells by interacting with their target mRNAs. Insulin receptor substrate 2 (IRS2) is one of the targets of miR-431 and can be regulated by ovarian hormones. However, the role of miR-431 and the associated signal transduction pathway in ovarian development has not been studied previously. In this study, we first analyzed the expression of miR-431 and IRS2 following stimulation with pregnant mare serum gonadotropin (PMSG) during the estrous cycle or different stages of ovarian development in mice. Subsequently, we investigated the role, function, and signaling pathway of miR-431 in the human granulosa cell line, COV434. The results showed that follicle stimulating hormone (FSH) gradually decreased miR-431 levels, induced IRS2, and promoted pAKT expression. Moreover, miR-431 overexpression and IRS2 knockdown attenuated AKT activation, inhibited cell proliferation, and decreased estradiol (E2) and progesterone (P4) synthesis. Further, luciferase reporter assay demonstrated that IRS2 was a direct target of miR-431. In conclusion, this study demonstrated that miR-431 regulates granulosa cell function through the IRS2/PI3K/AKT signaling pathway.

Downregulation of microRNA-431-5p promotes enteric neural crest cell proliferation via targeting LRSAM1 in Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease (HSCR) is characterized by missing of enteric neurons in the terminal areas of the whole gut, which is causally related to poor proliferation of enteric neural crest cells (ENCCs). Our aim is to explore how miR-431-5p interacts with its target gene in regulation of proliferation of ENCCs in HSCR. METHODS: Mouse model of HSCR was established by Benzalkonium chloride (BAC) treatment. Quantitative Real-time PCR and western blotting were performed to determine the miR-431-5p and the LRSAM1 expression in colon tissues of the HSCR group (n = 8) and the control group (n = 8) and in ENCCs isolated from colon tissues. CCK-8 assay was performed to detect the proliferation of ENCCs of HSCR. ENCCs after transfection with miR-431-5p mimics or miR-431-5p inhibitor. Luciferase reporter assay was conducted to clarify the connections between miR-431-5p and LRSAM1. RESULTS: Upregulation of miR-431-5p and downregulation of LRSAM1 were found in ENCCs of HSCR. Downregulation of miR-431-5p could promote cell proliferation of ENCCs. LRSAM1 was proved to be the target gene of miR-431-5p by luciferase reporter assay. Moreover, proliferation of ENCCs was increased in the miR-431-5p inhibitor group and was suppressed after knocking down LRSAM1. CONCLUSION: Downregulation of miR-431-5p promoted proliferation of ENCCs via targeting LRSAM1, which provides an innovative and candidate target for treatment of HSCR.

The role of miR-431-5p in regulating pulmonary surfactant expression in vitro.

BACKGROUND: Pulmonary surfactant is the complex mixture of lipid and protein that covers the alveolar surface. Pulmonary surfactant deficiency is one of the main causes of neonatal respiratory distress. Recent studies showed that miRNA plays an important role in lung development, but research into miR-431 regulation of pulmonary surfactant are sparse. In this study, we explored the regulatory role of miR-431-5p in the expression of pulmonary surfactant and identified its potential target gene, Smad4. METHODS: The bioinformatics tool TargetScan was used to predict the targets of miR-431. The expression of miR-431-5p was achieved via transfection of miR-431-5p mimics, an miR-431-5p inhibitor and corresponding negative control. The level of miR-431-5p was determined using quantitative real-time PCR. The CCK8 assay was conducted to confirm cell growth 12 h after transfection with miR-431-5p mimics, inhibitor or NC. Smad4 and surfactant-associated proteins in A549 were analyzed using western blot and quantitative real-time PCR. RESULTS: Smad4 was validated as a target of miR-431 in A549 cells. Overexpression of miR-431 accelerated A549 proliferation and inhibited A549 apoptosis. The mRNA and protein levels for the surfactant proteins (SP-A, SP-B, SP-C and SP-D) were found to be differentially expressed in A549 cells over- or under-expressing miR-431-5p. CONCLUSION: Our results show that miR-431-5p is critical for pulmonary surfactant expression and that its regulation is closely related to the TGF-ß/Smad4 pathway. These results will help us to study the pathophysiological mechanism of lung developmental diseases.

miR-431 is involved in regulating cochlear function by targeting Eya4.

To understand the relationship between microRNAs and hearing loss and help clarify the causes of hereditary deafness, we studied the functions of miR-431 in cochleae. We first investigated the spatial-temporal expression profiles of miR-431 in spiral ganglion neurons (SGNs) in cochleae using real-time PCR and miRNA in situ hybridization. These studies showed that expression of miR-431 was high in SGNs in the cochleae of newborn mice, and decreased as development progressed. To test the functional effects of miR-431, we established miR-431 overexpressing transgenic (Tg) mice. Surface preparations of the cochlear basilar membrane and cochlear sections revealed no major structural differences between Tg and wild-type (Wt) mice. However, a comparison of auditory brain stem responses (ABRs) in Tg and Wt mice showed that ABR thresholds were significantly higher in Tg mice than in Wt mice. Notably, the density of SGNs was significantly lower in Tg mice than in Wt mice. We also found that the proportion of mature SGNs in cultures of primary SGNs from Tg cochleae was lower and their axons were shorter. A bioinformatics analysis predicted that the mRNA target of miR-431 was Eya4, a finding confirmed by luciferase reporter assays and western blotting. Importantly, overexpression of miR-431 in cochleae of Tg mice inhibited the translation of Eya4 mRNA, leading to a deficiency of EYA4. Thus, excessive amounts of miR-431 in cochleae of Tg mice may be the cause of sparse SGNs, which in turn could be responsible for hearing loss.

Myostatin regulates miR-431 expression via the Ras-Mek-Erk signaling pathway.

MicroRNAs (miRNAs) play critical regulatory roles in controlling myogenic development both in vitro and in vivo; however, the molecular mechanisms underlying transcriptional regulation of miRNA genes in skeletal muscle cells are largely unknown. Here, using a microarray hybridization approach, we identified myostatin-regulated miRNA genes in skeletal muscle tissues by systematically searching miRNAs that are differentially expressed between wild-type and myostatin-null mice during development. We found that 116 miRNA genes were differentially expressed in muscles between these mice across different developmental stages. We further characterized myostatin-regulated miR-431 was upregulated in skeletal muscle tissues of myostatin-null mice. In functional studies, we found that overexpression of miR-431 in C2C12 myoblast cells attenuated myostatin-induced suppression of myogenic differentiation. Mechanistic studies further demonstrated that myostatin acted through the Ras-Mek-Erk signaling pathway to transcriptionally regulate miR-431 expression C2C12 cells. Our findings provide new insight into the mechanisms underlying transcriptional regulation of miRNA genes by myostatin during skeletal muscle development.

Functional role of circRNA CHRC through miR-431-5p/KLF15 signaling axis in the progression of heart failure.

Pathological myocardial hypertrophy is a common early clinical manifestation of heart failure, with noncoding RNAs exerting regulatory influence. However, the molecular function of circular RNAs (circRNAs) in the progression from cardiac hypertrophy to heart failure remains unclear. To uncover functional circRNAs and identify the core circRNA signaling pathway in heart failure, we construct a global triple network (microRNA, circRNA, and mRNA) based on the competitive endogenous RNA (ceRNA) theory. We observe that cardiac hypertrophy-related circRNA (circRNA CHRC), within the ceRNA network, is down-regulated in both transverse aortic constriction mice and Ang-II--treated primary mouse cardiomyocytes. Silencing circRNA CHRC increases cross-sectional cell area, atrial natriuretic peptide, and ß-myosin heavy chain levels in primary mouse cardiomyocytes. Further screening shows that circRNA CHRC targets the miR-431-5p/KLF15 axis implicated in heart failure progression in vivo and in vitro. Immunoprecipitation with anti-Ago2-RNA confirms the interaction between circRNA CHRC and miR-431-5p, while miR-431-5p mimics reverse Klf15 activation caused by circRNA CHRC overexpression. In summary, circRNA CHRC attenuates cardiac hypertrophy via sponging miR-431-5p to maintain the normal level of Klf15 expression.

Isoliquiritigenin regulates the circ_0002860/miR-431-5p/RAB9A axis to function as a tumor inhibitor in melanoma.

Background: Isoliquiritigenin (ISL) presents antitumor effects against melanoma cells. It is known that various circular RNAs (circRNAs) are involved in the development of melanoma. Therefore, the present study aims to investigate the molecular mechanisms of ISL and circ_0002860. Methods: Circ_0002860, microRNA-431-5p (miR-431-5p) and member RAS oncogene family (RAB9A) were detected through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. Cell viability was examined via cell counting kit-8 assay. The proliferation ability was assessed using colony formation assay. Cell apoptosis and cell cycle were determined by flow cytometry. Transwell assay was used for detection of migration and invasion. Western blot was conducted for protein analysis. Target binding was confirmed via dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In vivo research was performed through xenograft tumor assay. Results: Circ_0002860 was downregulated by ISL in melanoma cells. ISL-induced inhibitory effects on cell proliferation, cell cycle progression, migration and invasion were alleviated by circ_0002860 overexpression. MiR-431-5p was a target of circ_0002860. Circ_0002860 eliminated the ISL-induced tumor inhibition via sponging miR-431-5p in melanoma cells. Circ_0002860 elevated the RAB9A level by targeting miR-431-5p. The function of ISL was related to miR-431-5p/RAB9A axis in melanoma progression. Tumor growth was reduced by ISL in vivo through downregulating circ_0002860 to regulate miR-431-5p and RAB9A levels. Conclusion: The current data indicates that ISL suppressed cell malignant progression of melanoma via targeting the circ_0002860/miR-431-5p/RAB9A pathway.

CircRTN1 acts as a miR-431-5p sponge to promote thyroid cancer progression by upregulating TGFA.

PURPOSE: This study aimed to explore the role and underlying mechanism of circular RNA (circRNA) reticulon 1 (circRTN1) in thyroid cancer (TC). METHODS: The expression levels of circRTN1, microRNA-431-5p (miR-431-5p), and transforming growth factor-alpha (TGFA) mRNA were measured by quantitative real-time PCR (qRT-PCR). Cell proliferation was evaluated using colony formation and 5-ethynyl-2'-deoxyuridine (EdU) assays. Cell apoptosis was analyzed using flow cytometry. Cell migration and invasion were measured using the transwell assay. The protein levels of ki-67, Bax, matrix metalloproteinase 2 (MMP-2), and TGFA were detected using Western blot assay. The interaction between miR-431-5p and circRTN1 or TGFA was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The effect of circRTN1on TC in vivo was explored via xenograft tumor assay. RESULTS: The expression of circRTN1 was increased in TC tissues and cells. Knockdown of circRTN1 suppressed TC cell proliferation, migration, and invasion, and increased cell apoptosis. MiR-431-5p was a target of circRTN1, and miR-431-5p downregulation reversed the role of circRTN1 knockdown in TC cells. TGFA was identified as a direct target of miR-431-5p, and miR-431-5p exerted the anti-tumor role in TC cells by downregulating TGFA. Moreover, circRTN1 sponged miR-431-5p to regulate TGFA expression. Furthermore, circRTN1 knockdown inhibited tumor growth in vivo. CONCLUSION: CircRTN1 acted as a cancer-promoting circRNA in TC by regulating the miR-431-5p/TGFA axis, providing a potential therapeutic strategy for TC treatment.

CircPTTG1IP knockdown suppresses rheumatoid arthritis progression by targeting miR-431-5p/FSTL1 axis.

BACKGROUND: It is observed that circular RNA (circRNA) PTTG1 interacting protein (circPTTG1IP) level is notably up-regulated in rheumatoid arthritis (RA) patients by previous study. However, its precise role and working mechanism in RA pathology remain to be clarified. METHODS AND RESULTS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were carried out to examine RNA and protein expression. Cell proliferation was analyzed by colony formation assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay. Cell motility was assessed by transwell assays and wound healing assay. Flow cytometry (FCM) analysis was performed to assess cell apoptosis rate. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA-pull down assays were conducted to confirm the interaction between microRNA-431-5p (miR-431-5p) and circPTTG1IP or follistatin like 1 (FSTL1). CircPTTG1IP expression was up-regulated in the synovial tissues of RA patients and RA patients-derived fibroblast-like synoviocytes (RA-FLS). CircPTTG1IP absence suppressed the proliferation, migration, and invasion and induced the apoptosis of RA-FLS. CircPTTG1IP negatively regulated the expression of miR-431-5p by directly binding to it in RA-FLS. CircPTTG1IP interference-mediated effects in RA-FLS were largely counteracted by the silence of miR-431-5p. miR-431-5p directly interacted with the 3' untranslated region (3'UTR) of FSTL1. FSTL1 overexpression largely overturned miR-431-5p accumulation-mediated effects in RA-FLS. CircPTTG1IP positively regulated FSTL1 expression by sponging miR-431-5p in RA-FLS. CONCLUSION: CircPTTG1IP absence suppressed RA progression through mediating miR-431-5p/FSTL1 signaling cascade.

Identification of circRNA circ-CSPP1 as a potent driver of colorectal cancer by directly targeting the miR-431/LASP1 axis.

Colorectal cancer (CRC) is the third most common malignancy worldwide. Circular RNAs (circRNAs) have been implicated in cancer biology. The purpose of the current work is to investigate the precise parts of circRNA centrosome and spindle pole-associated protein 1 (circ-CSPP1) in the progression of CRC. Our data showed that circ-CSPP1 was significantly overexpressed in CRC tissues and cells. The knockdown of circ-CSPP1 attenuated cell proliferation, migration, invasion and promoted apoptosis in vitro and weakened tumor growth in vivo. circ-CSPP1 directly targeted miR-431, and circ-CSPP1 knockdown modulated CRC cell progression in vitro via upregulating miR-431. Moreover, LIM and SH3 protein 1 (LASP1) was a functional target of miR-431 in modulating CRC cell malignant progression. Furthermore, circ-CSPP1 in CRC cells functioned as a posttranscriptional regulator on LASP1 expression by targeting miR-431. Our present study identified the oncogenic role of circ-CSPP1 in CRC partially by the modulation of the miR-431/LASP1 axis, providing evidence for circ-CSPP1 as a promising biomarker for CRC management.