A large-scale microRNA transcriptome-wide association study identifies two susceptibility microRNAs, miR-1307-5p and miR-192-3p, for colorectal cancer risk.

Transcriptome-wide association studies (TWAS) have identified many putative susceptibility genes for colorectal cancer (CRC) risk. However, susceptibility miRNAs, critical dysregulators of gene expression, remain unexplored. We genotyped DNA samples from 313 CRC East Asian patients and performed small RNA sequencing in their normal colon tissues distant from tumors to build genetic models for predicting miRNA expression. We applied these models and data from genome-wide association studies (GWAS) including 23 942 cases and 217 267 controls of East Asian ancestry to investigate associations of predicted miRNA expression with CRC risk. Perturbation experiments separately by promoting and inhibiting miRNAs expressions and further in vitro assays in both SW480 and HCT116 cells were conducted. At a Bonferroni-corrected threshold of P < 4.5 × 10-4, we identified two putative susceptibility miRNAs, miR-1307-5p and miR-192-3p, located in regions more than 500 kb away from any GWAS-identified risk variants in CRC. We observed that a high predicted expression of miR-1307-5p was associated with increased CRC risk, while a low predicted expression of miR-192-3p was associated with increased CRC risk. Our experimental results further provide strong evidence of their susceptible roles by showing that miR-1307-5p and miR-192-3p play a regulatory role, respectively, in promoting and inhibiting CRC cell proliferation, migration, and invasion, which was consistently observed in both SW480 and HCT116 cells. Our study provides additional insights into the biological mechanisms underlying CRC development.

Effect of the SARS-CoV-2 Delta-associated G15U mutation on the s2m element dimerization and its interactions with miR-1307-3p.

The s2m, a highly conserved 41-nt hairpin structure in the SARS-CoV-2 genome, serves as an attractive therapeutic target that may have important roles in the virus life cycle or interactions with the host. However, the conserved s2m in Delta SARS-CoV-2, a previously dominant variant characterized by high infectivity and disease severity, has received relatively less attention than that of the original SARS-CoV-2 virus. The focus of this work is to identify and define the s2m changes between Delta and SARS-CoV-2 and the subsequent impact of those changes upon the s2m dimerization and interactions with the host microRNA miR-1307-3p. Bioinformatics analysis of the GISAID database targeting the s2m element reveals a >99% correlation of a single nucleotide mutation at the 15th position (G15U) in Delta SARS-CoV-2. Based on 1H NMR spectroscopy assignments comparing the imino proton resonance region of s2m and the s2m G15U at 19°C, we show that the U15-A29 base pair closes, resulting in a stabilization of the upper stem without overall secondary structure deviation. Increased stability of the upper stem did not affect the chaperone activity of the viral N protein, as it was still able to convert the kissing dimers formed by s2m G15U into a stable duplex conformation, consistent with the s2m reference. However, we show that the s2m G15U mutation drastically impacts the binding of host miR-1307-3p. These findings demonstrate that the observed G15U mutation alters the secondary structure of s2m with subsequent impact on viral binding of host miR-1307-3p, with potential consequences on immune responses.

Associations of RPEL1 and miR-1307 gene polymorphisms with disease susceptibility, glucocorticoid efficacy, anxiety, depression, and health-related quality of life in Chinese systemic lupus erythematosus patients.

OBJECTIVE: Our present study intended to examine the associations of RPEL1 and miR-1307 gene polymorphisms (rs4917385 and rs7911488) with susceptibility, glucocorticoids (GCs) efficacy, anxiety, depression, and health-related quality of life (HRQoL) in Chinese systemic lupus erythematosus (SLE) patients. METHODS: Initially, 1000 participants (500 SLE cases and 500 controls) were recruited for the case-control study. Then, 429 cases who received GCs were followed through 12 weeks to explore GCs efficacy, depression, anxiety, and HRQoL. We selected the iMLDR technique for genotyping: RPEL1: rs4917385 (G/T) and miR-1307: rs7911488 (A/G). RESULTS: The minor G allele of rs7911488 reduced the risk of SLE (p = .024). Four haplotypes consisting of rs4917385 and rs7911488 were associated with SLE susceptibility (p < .025). Both rs4917385 and rs7911488 were associated with anxiety symptoms and physical function (PF) in SLE patients (p < .025). The rs4917385 was associated with depression and its improvement. No statistical significance was found between RPEL1 and miR-1307 gene polymorphisms with GCs efficacy. Meanwhile, additive interaction analysis showed a significant association between RPEL1 and miR-1307 gene polymorphisms with tea consumption in anxiety. CONCLUSION: RPEL1 and miR-1307 gene polymorphisms (rs4917385 and rs7911488) might be related to SLE susceptibility in Chinese population. Additionally, the two polymorphisms were possibly associated with depression, anxiety, and HRQoL in Chinese SLE population.

Hypoxia-driven miR-1307-3p promotes hepatocellular carcinoma cell proliferation and invasion by modulating DAB2 interacting protein.

Hypoxia is a common feature of the solid tumor microenvironment that is presented as poor clinical outcomes in multiple tumor types, including HCC. Hypoxia stabilizes HIF-1α/HIF-2α, which then moves into the nucleus and binds with HIF-1ß to form a transcription complex, thereby promoting the transcription of target genes, including mRNAs, miRNAs and lncRNAs to exert their biological functions. Here, through a series of functional assay, including hypoxia culture, MTT, colony-formation, Transwell, qRT-PCR and western blot, we confirmed that miR-1307-3p, as a novel hypoxia-responsive factor, can be directly transcribed by HIF-1α rather than HIF-2α. Hypoxia-driven miR-1307-3p facilitated proliferation and invasion of HCC cells via repressing DAB2IP. Moreover, under hypoxia microenvironment, DAB2IP, as a direct target of miR-1307-3p, was down-regulated to activate AKT/mTOR signaling to further maintain the expression level of HIF-1α, thereby forming a feedback loop between HIF-1α/miR-1307-3p and DAB2IP. Targeting miR-1307-3p/DAB2IP axis also modulated tumor growth and metastasis in vivo. In summary, there exists a feedback loop between HIF-1α/miR-1307-3p and DAB2IP in HCC. Targeting a vicious feedback loop between HIF-1α/miR-1307-3p and DAB2IP may be a promising strategy to combat HCC.

Engineered exosome-mediated delivery of circDIDO1 inhibits gastric cancer progression via regulation of MiR-1307-3p/SOCS2 Axis.

BACKGROUND: Our previous study has identified a novel circRNA (circDIDO1) that is down-regulated in gastric cancer (GC) and significantly inhibits GC progression. The purpose of this study is to identify the molecular mechanism for circDIDO1 and to evaluate the therapeutic effect of circDIDO1 in GC. METHODS: By combining bioinformatic analysis with RNA sequencing data, we predicted the potential target of circDIDO1 and further validated the regulatory mechanisms for its tumor suppressor function in GC. RIP assay, luciferase reporter assay and in vitro cell function assays were performed to analyze circDIDO1-regulated downstream target genes. For the therapeutic study, circDIDO1-loaded, RGD-modified exosomes (RGD-Exo-circDIDO1) were constructed and its anti-tumor efficacy and biological safety were evaluated in vitro and in vivo. RESULTS: CircDIDO1 inhibited GC progression by regulating the expression of the signal transducer inhibitor SOSC2 through sponging miR-1307-3p. Overexpression of circDIDO1 or SOSC2 antagonized the oncogenic role of miR-1307-3p. RGD-Exo-circDIDO1 could efficiently deliver circDIDO1 to increase SOCS2 expression in GC cells. Compared with PBS and RGD-Exo-vector treatment, RGD-Exo-circDIDO1 treatment significantly inhibited the proliferation, migration and invasion of GC cells while promoted cell apoptosis. The therapeutic efficacy of RGD-Exo-circDIDO1 was further confirmed in a mouse xenograft tumor model. In addition, major tissues including the heart, liver, spleen, lungs and kidneys showed no obvious histopathological abnormalities or lesions in the RGD-Exo-circDIDO1 treated group. CONCLUSION: Our findings revealed that circDIDO1 suppressed the progression of GC via modulating the miR-1307-3p/SOSC2 axis. Systemic administration of RGD modified, circDIDO1 loaded exosomes repressed the tumorigenicity and aggressiveness of GC both in vitro and in vivo, suggesting that RGD-Exo-circDIDO1 could be used as a feasible nanomedicine for GC therapy.

miR-1307-5p suppresses proliferation and tumorigenesis of bladder cancer via targeting MDM4 and the Hippo signaling pathway.

BACKGROUND: Emerging evidence has shown that miR-1307-5p is involved in tumorigenesis of various types of cancer. This study aims to assess the role and mechanism of miR-1307-5p in bladder cancer. METHODS: Bioinformatics analyses were carried out with clinical datasets in the public domains. To investigate the cellular functions of miR-1307-5p, assays of cell proliferation, cell cycle and cell apoptosis were conducted in bladder cancer cell lines and xenografts. The molecular mechanisms of miR-1307-5p were studied using luciferase reporter, RT-qPCR, and western blotting analyses. RESULTS: We found that miR-1307-5p expression was significantly decreased in bladder cancer tissues, and its lower level was associated with poor prognosis. Cellular assays indicated the tumor-suppressor roles of miR-1307-5p were linked to cell proliferation, cell cycle inhibition, and cell apoptosis promotion. Conversely, anti-miR-1307-5p facilitated cell proliferation and cell cycle and antagonized cell apoptosis. In the in vivo setting, tumor growth was suppressed by miR-1307-5p overexpression. We found by bioinformatic and luciferase reporter assays that miR-1307-5p targets the 3'-UTR of MDM4, a well-known Inhibitor of TP53-mediated transactivation, cell cycle arrest and apoptosis. Specifically, miR-1307-5p markedly reduced MDM4 proteins expression, decreased the expression of Ki-67 and PCNA, and increased the expression of cleaved-caspase 3 and caspase 9. While in parallel assays, anti-miR-1307-5p had opposite effects. In addition, we found that miR-1307-5p overexpression would suppress bladder cancer cell growth by inhibiting MDM4 and its downstream Hippo pathway. CONCLUSION: In bladder cancer, miR-1307-5p functions as a tumor suppressor and has the potentials as biomarker and therapeutical agent.

Circular RNA CircPPP1CB Suppresses Tumorigenesis by Interacting With the MiR-1307-3p/SMG1 Axis in Human Bladder Cancer.

Circular RNA (circRNA) is a newly discovered endogenous non-coding RNA (ncRNA), which is characterized with a closed circular structure. A growing body of evidence has verified the vital roles of circRNAs in human cancer. In this research, we selected circPPP1CB as a study object by circRNA sequencing and quantitative real-time PCR (qRT-PCR) validation in human bladder cancer (BC). CircPPP1CB is downregulated in BC and is negatively correlated with clinical stages and histological grades. Functionally, circPPP1CB modulated cell growth, metastasis, and epithelial-to-mesenchymal transition (EMT) process in vitro and in vivo. Mechanically, we performed various experiments to verify the circPPP1CB/miR-1307-3p/SMG1 regulatory axis. Taken together, our results demonstrated that circPPP1CB participates in tumor growth, metastasis, and EMT process by interacting with the miR-1307-3p/SMG1 axis, and that circPPP1CB might be a novel therapeutic target and diagnostic biomarker in human BC.

Pathogenesis and Molecular Mechanisms of Anderson-Fabry Disease and Possible New Molecular Addressed Therapeutic Strategies.

Anderson-Fabry disease (AFD) is a rare disease with an incidenceof approximately 1:117,000 male births. Lysosomal accumulation of globotriaosylceramide (Gb3) is the element characterizing Fabry disease due to a hereditary deficiency α-galactosidase A (GLA) enzyme. The accumulation of Gb3 causes lysosomal dysfunction that compromises cell signaling pathways. Deposition of sphingolipids occurs in the autonomic nervous system, dorsal root ganglia, kidney epithelial cells, vascular system cells, and myocardial cells, resulting in organ failure. This manuscript will review the molecular pathogenetic pathways involved in Anderson-Fabry disease and in its organ damage. Some studies reported that inhibition of mitochondrial function and energy metabolism plays a significant role in AFD cardiomyopathy and in kidney disease of AFD patients. Furthermore, mitochondrial dysfunction has been reported as linked to the dysregulation of the autophagy-lysosomal pathway which inhibits the mechanistic target of rapamycin kinase (mTOR) mediated control of mitochondrial metabolism in AFD cells. Cerebrovascular complications due to AFD are caused by cerebral micro vessel stenosis. These are caused by wall thickening resulting from the intramural accumulation of glycolipids, luminal occlusion or thrombosis. Other pathogenetic mechanisms involved in organ damage linked to Gb3 accumulation are endocytosis and lysosomal degradation of endothelial calcium-activated intermediate-conductance potassium ion channel 3.1 (KCa3.1) via a clathrin-dependent process. This process represents a crucial event in endothelial dysfunction. Several studies have identified the deacylated form of Gb3, globotriaosylsphingosine (Lyso-Gb3), as the main catabolite that increases in plasma and urine in patients with AFD. The mean concentrations of Gb3 in all organs and plasma of Galactosidase A knockout mice were significantly higher than those of wild-type mice. The distributions of Gb3 isoforms vary from organ to organ. Various Gb3 isoforms were observed mainly in the kidneys, and kidney-specific Gb3 isoforms were hydroxylated. Furthermore, the action of Gb3 on the KCa3.1 channel suggests a possible contribution of this interaction to the Fabry disease process, as this channel is expressed in various cells, including endothelial cells, fibroblasts, smooth muscle cells in proliferation, microglia, and lymphocytes. These molecular pathways could be considered a potential therapeutic target to correct the enzyme in addition to the traditional enzyme replacement therapies (ERT) or drug chaperone therapy.

miR-1307-5p regulates proliferation and apoptosis of chondrocytes in osteoarthritis by specifically inhibiting transforming growth factor beta-induced gene.

OBJECTIVE: To explore the effect of miR-1307-5p which specifically inhibits transforming growth factor beta-induced gene (TGFBI) on the biologic behavior of osteoarthritis (OA) chondrocytes. METHODS: We detected miR-1307-5p and TGFBI expression in the cartilage tissue specimens of OA patients and mice, respectively. RNA22 was applied to predict the target gene of miR-1307-5p, and we further verified the relationship by performing a dual luciferase reporter experiment. Enzyme-linked immunosorbent assay was used to measure the expression of matrix metalloproteinase inhibitor-1 (TIMP-1), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the culture medium of mouse chondrocytes. Quantitative reverse transcription-polymerase chain reaction and western blot were used to measure the expression of Bax and Bcl-2. MTT method was applied to detect the proliferation activity of chondrocytes, while flow cytometry was implemented to detect the apoptosis of chondrocytes. RESULTS: The expression of miR-1307-5p in cartilage tissue specimens of OA patients was up-regulated, while TGFBI expression was down-regulated. Compared with normal mice cartilage tissue specimens, the expression of miR-1307-5p in cartilage tissue specimens of OA mouse was increased, while TGFBI expression was decreased (both P<0.05). The results of the dual luciferase reporter experiment showed that TGFBI was a target gene of miR-1307-5p. In cell experiments, compared with the normal group, TIMP-1 and Bcl-2 expression, and cell proliferation activities in all model groups were decreased. IL-1ß, IL-6, TNF-α, Bax expression, and cell apoptosis rates were increased (all P<0.05). Compared with the blank group, TIMP-1 and Bcl-2 expression, and cell proliferation activities in the miR-1307-5p inhibitor group and the TGFBI group were increased, while IL-1ß, IL-6, TNF-α, and Bax expression, and cell apoptosis rates were decreased (all P<0.05). The changes in all indicators in the miR-1307-5p mimic group were opposite to those of the miR-1307-5p inhibitor group (all P<0.05). There were no significant differences concerning all indicators between the blank group and the NC group, and between the blank group and the miR-1307-5p mimic + TGFBI group (all P>0.05). CONCLUSION: The suppression of miR-1307-5p expression can increase TGFBI expression, promoting the proliferation of chondrocytes in OA mice, while inhibiting their apoptosis.

The effect of dexmedetomidine on biological behavior of osteosarcoma cells through miR-1307 expression.

OBJECTIVES: This study analyzed the effect of dexmedetomidine (DEX) on biological behavior of osteosarcoma cells through expression of miR-1307. METHODS: We performed routine culture of human osteosarcoma cells MG-63 and randomly divided into control group, low-dose DEX group (25 ng/ml), medium-dose DEX group (50 ng/ml) and high-dose DEX group (100 ng/ml). Subsequently, we detected the cell proliferation (by CCK8 method), cell apoptosis (flow cytometry), mir-1307 expression (qRT-PCR), cell invasion (Transwell), and cell migration (scratch test) respectively. RESULTS: The growth rate of osteosarcoma cells MG-63 slowed down with the increase of DEX concentration. Compared with the control group, the cellular absorbance in groups with different DEX dose decreased remarkably after 72 hours of culture (P<0.05). The proportion of apoptotic cells increased as well with the uplifting of DEX concentration, and the apoptotic rate in medium and high dosed DEX groups were remarkably higher than which in control group (P<0.05). Compared with the control group, the invasive ability of MG-63 cells after DEX treatment decreased significantly, and with the increase of DEX concentration, the number of invasive cells declined more obviously (P<0.05). Compared with the control group, the mobility rate of MG-63 cells after DEX treatment decreased significantly, and with the increase of DEX concentration, the cell mobility rate decreased more remarkably (P<0.05). In addition, the relative expression of miR-1307 in MG-63 cells after DEX treatment decreased significantly comparing to the control group, and the decline was more noteworthy with the increase of DEX concentration (P<0.05). CONCLUSION: DEX can effectively inhibit the proliferation, invasion, metastasis, and apoptosis of osteosarcoma cells in a dose-dependent manner, and its efficacy may be related to its regulation of miR-1307 expression.

Upregulation of miR-1307-3p and its function in the clinical prognosis and progression of gastric cancer.

Gastric cancer is one of the major causes of cancer-associated mortality worldwide. miR-1307-3p has been demonstrated to serve multiple roles in the development of various types of cancer. The present study aimed to evaluate the expression and functional role of miR-1307-3p in the progression of gastric cancer. The expression of miR-1307-3p in gastric cancer tissues and cell lines was detected by reverse transcription quantitative PCR. Furthermore, the correlation between miR-1307-3p expression and the clinicopathological characteristics and prognosis of patients was evaluated. Cell Counting Kit-8 and Transwell assays were performed to analyze the effects of miR-1307-3p on the proliferation and the migratory and invasive abilities of gastric cancer cells, respectively. Dual-luciferase reporter assay was conducted to reveal the potential underlying mechanism of miR-1307-3p. In gastric cancer tissues and cells, miR-1307-3p expression was significantly upregulated compared with the normal tissues and cell lines. In addition, the expression of miR-1307-3p was associated with the Tumor-Node Metastasis stage of patients. The results from Cox regression analysis demonstrated that miR-1307-3p may serve as an independent predictor for the prognosis of patients with gastric cancer. Furthermore, the upregulation of miR-1307-3p in gastric cancer cell lines significantly promoted the cell proliferation and migratory and invasive abilities by targeting DAB2 interacting protein. In conclusion, the findings from the present study suggested that miR-1307-3p may serve as a tumor promoter of gastric cancer and that miR-1307-3p expression in tumor tissues may be used as a prognostic indicator for patients with gastric cancer.

miR-1307-3p overexpression inhibits cell proliferation and promotes cell apoptosis by targeting ISM1 in colon cancer.

BACKGROUND: colon adenocarcinoma (COAD) is the most common malignant tumor of gastrointestinal tract. Our study attempts to explore the effect of miR-1307-3p on biological function of COAD cells and its connection with isthmin 1 (ISM1). METHODS: The miRNA dataset and clinical information of patients with COAD were downloaded from The Cancer Genome Atlas (TCGA) database. The survival prognosis was analyzed by GGSURV package from R. MicroRNA (miR)-1307-3p was identified by identifying overlapping miRNAs that target ISM1, across two databases (miRDB and Targetscan). Dual luciferase reporter assay was employed to scrutinize the relationship between miR-1307-3p and ISM1. RT-PCR was used to quantify miR-1307-3p and ISM1 expression of colon cancer tissues and cell lines. Western blot was performed to quantify related protein expression. Flow Cytometry, CCK8 and colony formation assays were performed to evaluate the apoptosis, cell cycle, cell viability and proliferation of COAD cells. RESULTS: miR-1307-3p mRNA level decreased in both COAD tissues and cell lines. Overexpression of miR-1307-3p suppressed the proliferation, promoted apoptosis and arrested cell cycle at G1 phase, meanwhile, downregulation of ISM1 accelerated the proliferation, inhibited apoptosis and promote cell cycleprogression. The result of dual luciferase reporter assay indicated that miR-1307-3p targeted ISM1 directly and inhibited its expression. The functions of miR-1307-3p regulating cleaved caspase-3, cyclinD1, Ki67 protein levels and activation of Wnt3a/ß-catenin signaling pathway were reversed by ISM1. CONCLUSIONS: miR-1307-3p inhibited activation of Wnt3a/ß-catenin signaling through targeting downregulation of ISM1, thereby inhibited proliferation and promote apoptosis of COAD cells.

MiR-1307 influences the chemotherapeutic sensitivity in ovarian cancer cells through the regulation of the CIC transcriptional repressor.

BACKGROUND: Extended from our previously observation that expression of miR-1307 in chemoresistant primary ovarian cancer tissues is elevated, here we are aiming to dissect the function of miR-1307 and its predicted target gene, CIC (capicua transcriptional repressor), in ovarian cancer chemotherapy. METHODS: We evaluated the expression of miR-1307 and CIC in chemoresistant and chemosensitive ovarian cancer tissues and cells by real time-PCR and western blot. We used chemoresistant/chemosensitive cells with miR-1307 suppression/overexpression to study the biological effects of miR-1307 by MTT and flow cytometer. Dual luciferase reporter gene assay was used to validate direct binding between miR-1307 and the 3'-UTR of CIC. Real-time PCR and western blot analyses, MTT and flow cytometry were used to reveal the biological effects of miR-1307 and CIC, as well as their regulation. RESULTS: We found that miR-1307 affects cell cycle dynamics, cell viability in ovarian cancer cells. In addition, its expression level can influence chemosensitivity to paclitaxel in ovarian cancer cells. We also validate that CIC is a downstream target of miR-1307 via its regulation on 3'-UTR of CIC gene and ETV4 and ETV5 are also regulated by miR-1307/CIC axis. CONCLUSIONS: Our data suggested that miR-1307 may be involved in the resistance of ovarian cancer to chemotherapy drugs via regulation of CIC, and should be further explored as a potential therapeutic target.

Host microRNA miR-1307 suppresses foot-and-mouth disease virus replication by promoting VP3 degradation and enhancing innate immune response.

MicroRNAs (miRNAs) play important regulatory roles during interactions between virus pathogens and host cells, but whether and how they work in the case of foot-and-mouth disease virus (FMDV) is less understood. Based on a microarray-based miRNA profiling in the porcine kidney cell line PK-15, we identified 36 differentially expressed host miRNAs at the early stage of FMDV infection, among which miR-1307 was significantly induced. Functional characterization demonstrated that miR-1307 attenuated FMDV replication. Further experiments proved that miR-1307 specifically promoted the degradation of the viral structural protein VP3 indirectly through proteasome pathway. Moreover, innate immune signaling was activated and expression of immune responsive genes was significantly enhanced in the miR-1307-overexpressing clones. Together, our data demonstrated that miR-1307 suppresses FMDV replication by destabilizing VP3 and enhancing host immune response. Importantly, subcutaneous injection of miR-1307 agomir delayed the FMDV-induced lethality in suckling mice, exhibiting its therapeutic potential to control foot-and-mouth disease (FMD).

hsa_circ_0091570 acts as a ceRNA to suppress hepatocellular cancer progression by sponging hsa-miR-1307.

Alterations in circular RNA (circRNA) expression have a vital impact on the biological processes in cancer. Moreover, the expression pattern and roles of circRNAs in hepatocellular cancer (HCC) remain unclear. This study performed qRT-PCR to determine the regulated circRNAs in HCC tissues and cell lines. CCK8, 5-ethynyl-2'-deoxyuridine (EdU) assay, colony formation, cell cycle assay, apoptotic assay, transwell, and wound healing assay were conducted to assess the function of hsa_circ_0091570 or miR-1307 on cell proliferation, apoptosis, and migration in vitro. Mouse xenograft models were used to measure the functions of hsa_circ_0091570 in vivo. The decreased expression of hsa_circ_0091570 was associated with the pathological staging of HCC patients. Furthermore, inhibition of hsa_circ_0091570 promoted cell proliferation and migration, blocked cell apoptosis in HCC cell lines, and promoted tumor growth in the mouse xenograft model. RNA immunoprecipitation assay verified the interaction of hsa_circ_0091570 and miR-1307. The miR-1307 inhibitor inhibited the function induced by hsa_circ_0091570 siRNA. Overall, hsa_circ_0091570 sponge miR-1307 as a ceRNA and regulate ISM1 expression by exerting functional roles in HCC.

miR-1307-3p promotes tumor growth and metastasis of hepatocellular carcinoma by repressing DAB2 interacting protein.

Increasing studies provide evidence to support that microRNAs (miRNAs) play important roles in regulating hepatocellular carcinoma (HCC) initiation and progression. However, whether miR-1307-3p is aberrantly expressed in HCC and affects malignant behaviors of cancer cells remain unknown. In this study, we found that miR-1307-3p expression was obviously up-regulated in HCC compared to adjacent nontumor tissues. Moreover, miR-1307-3p expression was prominently higher in HCC cells compared with the normal hepatic cell line LO2. Patients with venous infiltration, tumor size ≥5 cm and advanced tumor stages (III + IV) had significant higher levels of miR-1307-3p in HCC tissues. Notably, the high level of miR-1307-3p predicted poor clinical outcomes of HCC patients. Functionally, miR-1307-3p knockdown inhibited the proliferation, migration and invasion of MHCC97H and HCCLM3 cells, and suppressed the in vivo growth and metastasis of HCCLM3 cells. Conversely, overexpression of miR-1307-3p facilitated Hep3B cell proliferation, migration and invasion. Mechanistically, DAB2 interacting protein (DAB2IP) was screened as a direct target of miR-1307-3p. The expression of DAB2IP mRNA was down-regulated and inversely correlated with miR-1307-3p level in HCC tissues. miR-1307-3p knockdown increased the level of DAB2IP in HCC cells. Luciferase reporter assay confirmed the direct interaction between miR-1307-3p and 3'UTR of DAB2IP. Importantly, DAB2IP overexpression significantly suppressed the proliferation, migration and invasion of HCCLM3 cells. DAB2IP knockdown rescued miR-1307-3p silencing-attenuated HCC cell proliferation, migration and invasion. Taken together, our findings suggest that miR-1307-3p plays a driving role in HCC progression by targeting DAB2IP. Our study may provide new therapeutic targets for HCC treatment.

miR-1307-3p Stimulates Breast Cancer Development and Progression by Targeting SMYD4.

Recent studies show that dysregulated miRNAs play an important role in breast cancer initiation and progression. Here, we identified upregulated expression of miR-1307-3p in breast cancer tissues and that increased level of miR-1307-3p was closely correlated with lower survival rate in breast cancer patients. Consistent with clinical data, our in vitro data show that expression level of miR-1307-3p was significantly increased in breast cancer cell lines compared to human mammary epithelial cell line MCF10A. Overexpression of miR-1307-3p in MCF10A stimulated cell proliferation and caused their growth in soft agar and tumor formation in nude mice. In contrast, inhibition of miR-1307-3p suppressed breast cancer cell proliferation and their growth in soft agar and inhibited tumor formation in nude mice. Further, we identified that miR-1307-3p plays its oncogenic role through targeting SET and MYND domain-containing 4 (SMYD4) expression in breast cancer. Taken together, our findings suggest that miR-1307-3p is a oncogenic miRNA that significantly contributes to breast cancer development and progression, and inhibition of miR-1307-3p may be a novel strategy for inhibits breast cancer initiation and progression.

Mir-1307 regulates cisplatin resistance by targeting Mdm4 in breast cancer expressing wild type P53.

BACKGROUND: Many chemotherapy regimens are used to treat breast cancer; however, breast cancer cells often develop drug resistance that usually leads to relapse and poor prognosis. MicroRNAs (miRNAs) are short non-coding RNA molecules that post-transcriptionally regulate gene expression and play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. We investigated the roles of miRNAs in the development of drug resistance in human breast cancer cells. METHODS: MiRNA expression was detected in human breast cancer cell lines MCF-7 and MDA-MB-468 via real time PCR; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide, cell viability, colony formation, and luciferase reporter gene assays; Western blot; and immunohistochemistry. RESULTS: MiR-1307 was downregulated while MDM4 was upregulated in MCF-7/cisplatin (CDDP) and MDA-MB-468/CDDP cells compared with parental MCF-7 and MDA-MB-468 cells. in vitro drug sensitivity assay demonstrated that overexpression of miR-1307 sensitized MCF-7/CDDP cells to CDDP. Luciferase activity assay with a reporter containing sequences from the 3' untranslated region of Mdm4 in MCF-7/CDDP cells suggested that Mdm4 was the direct target gene of miR-1307. Ectopic miR-1307 expression reduced the MDM4 protein level and sensitized MCF-7/CDDP cells to CDDP-induced apoptosis. CONCLUSION: Our findings suggest, for the first time, that miR-1307 could play a role in the development of CDDP resistance in breast cancer, at least in part by modulating apoptosis by targeting Mdm4.

Rs7911488 modified the efficacy of capecitabine-based therapy in colon cancer through altering miR-1307-3p and TYMS expression.

Capecitabine is an orally administered prodrug of 5-fluouracil (5-FU) and is used in first-line treatment of metastatic colorectal cancer. Studies have demonstrated that polymorphisms in 5-FU related ADME genes are associated with the efficacy of capecitabine. However, the relationship between the polymorphisms within the microRNA precursors and the efficacy of capecitabine is still largely unknown. We detected six polymorphisms in 274 colon cancer patients and statistically analyzed the association of the genotypes with the efficacy of capecitabine-based chemotherapy. The mechanisms underlying the effect of genotypes on the efficacy of capecitabine were also studied. We identified a polymorphism rs7911488 T>C in pre-miR-1307 to be significantly associated with the efficacy of capecitabine chemotherapy in colon cancer patients. The response rates of capecitabine chemotherapy for the patients with TT, TC, and CC genotypes were 44.35% (55/124), 51.33% (58/113), and 24.32% (9/37), respectively. In the C-allelic patients, miR-1307-3p is down-regulated and TYMS, a direct target of miR-1307-3p, is over-expressed, which leads to insensitivity of cancer cells to capecitabine chemotherapy. The cancer cells with rs7911488 C allele were further observed to be resistant to 5-FU treatment in vitro and in vivo. Our findings show that rs7911488 C-allelic pre-miR-1307 leads to attenuated miR-1307-3p and elevated TYMS, thus insensitive to capecitabine chemotherapy in colon cancer.

miR-1307 promotes the proliferation of prostate cancer by targeting FOXO3A.

microRNAs have emerged as important regulators in various cancers, including prostate cancer. In this study, we investigated the role of miR-1307 in cell proliferation of prostate cancer. We found miR-1307 was overexpressed in prostate cancer cells and tissues, overexpression of miR-1307 significantly promoted cell proliferation and tumorigenesis in vitro investigated by MTT assay, colony formation assay and soft agar growth assay, meanwhile overexpression of miR-1307 inhibited cell cycle inhibitors p21 and p27 both in mRNA and protein levels. Knockdown of miR-1307 reduced these effects, confirming miR-1307 promotes prostate cancer cell proliferation. FOXO3A (Forkhead box protein O3a) was the target of miR-1307, miR-1307 directly bound to the 3'UTR of FOXO3A. Simultaneous knockdown of miR-1307 and FOXO3A promoted cell proliferation of prostate cancer. In summary, our results suggested miR-1307 contributed to prostate cancer proliferation by targeting FOXO3A.