Circ_0021350 plays an oncogene role by regulating miR-1207-3p/PIK3R3 in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most malignant glioma, with poor survival rates and prognosis. Several studies have reported the abnormal expression of circular RNAs (circRNAs) and their functions in the malignant biological behavior of GBM. However, such research is still in the preliminary stages, and further study is needed to confirm the therapeutic potential of circRNAs in GBM. METHODS: RNA-seq was performed using four tumor tissues from patients with GBM and their adjacent non-tumor brain tissues to screen differentially expressed circRNAs. Fluorescence in situ hybridization assay was used to examine the location of circ_0021350 in glioma cells. In addition, a series of biological function assays were employed to verify the oncogenic role of circ_0021350 in GBM. Quantitative reverse transcription PCR was used to examine circular, micro- (miRNA), and messenger RNA (mRNA) levels. Furthermore, dual-luciferase reporter, RNA pull-down, and RNA binding protein immunoprecipitation assays were applied to verify the interaction between circ_0021350 and its downstream effectors. RESULTS: Circ_0021350 was significantly elevated in GBM tissues and glioma cells. Overexpression of circ_0021350 promoted glioma cell proliferation and metastatic ability; silencing of circ_0021350 had the opposite effect. Mechanistic analysis revealed that circ_0021350 sponged miR-1207-3p to regulate PIK3R3, whose overexpression reversed the reduction in the malignant biological behavior of glioma cells caused by silencing circ_0021350. CONCLUSION: Our findings suggest that circ_0021350 is an oncogenic circRNA in GBM, and the circ_0021350/miR-1207-3p/PIK3R3 axis may serve as a potential therapeutic target in GBM treatment.

Knockdown of LINC01138 protects human chondrocytes against IL-1ß-induced damage by regulating the hsa-miR-1207-5p/KIAA0101 axis.

INTRODUCTION: Long intergenic non-protein coding RNA 1138 (LINC01138) plays a vital role in human cancers. In this study, we aimed to investigate the effect of LINC01138 on the progression of osteoarthritis (OA) and explore its potential mechanism of action. METHODS: The expression of LINC01138, hsa-miR-1207-5p, and KIAA0101 in OA tissues and normal tissues was analyzed using GSEA datasets and confirmed in human specimens. Human chondrocytes were treated with interleukin (IL)-1ß to establish an OA cell model. Quantitative real time PCR(qRT-PCR), enzyme-linked immunosorbent assay, and western blotting analyses were performed to evaluate the role of LINC01138, hsa-miR-1207-5p, and KIAA0101 during extracellular matrix (ECM) protein degeneration and cellular inflammatory response. The target relationship was predicted using DIANA-TarBase and TargetScan. The binding effects were verified by dual-luciferase reporter assay. RESULTS: LINC01138 expression was higher in OA tissues than in normal controls. LINC01138 levels increased in chondrocytes treated with IL-1ß. Silencing of LINC01138 attenuated the IL-1ß-induced decrease in Col2α1, aggrecan, and sulphated glycosaminoglycan (sGAG), and inhibited the IL-1ß-induced increase in matrix metalloproteinase (MMP)-13, IL-6, and tumor necrosis factor (TNF)-α. miR-1207-5p is weakly expressed in OA tissues and cell models. The inhibition of hsa-miR-1207-5p, a target of LINC01138, attenuated the effects of LINC01138 silencing on chondrocyte ECM degeneration and inflammatory responses. Silencing KIAA0101, a target of hsa-miR-1207-5p, alleviated the effect of hsa-miR-1207-5p on chondrocyte ECM degeneration and inflammatory responses. Furthermore, silencing of KIAA0101 inhibited the JAK/STAT and Wnt signaling pathways. CONCLUSION: Silencing LINC01138 protected chondrocytes from IL-1ß-induced damage, possibly by regulating the hsa-miR-1207-5p/KIAA0101 axis.

LncRNA PVT1 Regulates miR-1207-5p to Affect Colon Cancer Proliferation and Migration via the Wnt6/ß-catenin2 Pathway.

Background: We aimed to evaluate the effects of lncRNA PTV1 on colon cancer proliferation and migration via the Wnt6/ß-catenin2 pathway. Materials and Methods: A total of 117 colon cancer and normal adjacent tissue samples were collected. LncRNA PVT1 and miR-1207-5p expressions in these samples and colon cancer cell lines were detected by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR). LncRNA PVT1-silencing cells and miR-1207-5p-overexpressing Caco-2-siPVT1 cells were constructed, respectively. The effects of lncRNA PVT1 silencing on cell proliferation were assessed by MTT and colony formation assays. The effects on invasion and migration were tested by Transwell and scratch assays respectively. The targeting regulatory relationship between miR-1207-5p and Wnt6 was analyzed by a dual-luciferase reporter assay. The relationship between lncRNA PVT1 and miR-1207-5p was studied by RNA-binding protein immunoprecipitation and RNA pull-down assays. The expressions of proteins in the Wnt6/ß-catenin2 pathway were detected by Western blotting. Results: The lncRNA PVT1 mRNA expression in colon cancer tissue was significantly higher than that in normal adjacent tissue (p < 0.05). The expression in lncRNA PVT1-silencing cells was significantly down-regulated (p < 0.05). The colonies of Caco-2-siPVT1 cells decreased, accompanied by a reduced number of cells penetrating Matrigel and migration (p < 0.05). Compared with siPVT1 + NC group, the number of colonies and migration of siPVT1 + miR-1207-5p-overexpressing group increased significantly (p < 0.05). There was a targeting relationship between miR-1207-5p and PVT1. MiR-1207-5p had a targeted binding site with Wnt6. The protein expressions of Wnt6/ß-catenin2 in Caco-2-siPVT1 group were significantly lower than those of control and Caco-2-siNC groups (p < 0.05). Conclusion: LncRNA PVT1 was highly expressed in colon cancer. It may enhance the proliferation and migration of colon cancer cells by up-regulating miR-1207-5p level and enhancing the Wnt6/ß-catenin2 pathway.

Long non-coding RNA LUADT1 promotes nasopharyngeal carcinoma cell proliferation and invasion by downregulating miR-1207-5p.

Nasopharyngeal carcinoma (NPC) is a typical type of malignant tumor. This research paper aims to study the function and mechanism of long non-coding RNA lung adenocarcinoma-related transcript 1 (lncRNA-LUADT1) in the progression of NPC. In this study, the expressions of lncRNA-LUADT1, miR-1207-5p, and TEAD1 in NPC tissues and cell lines were detected by RT-qPCR. Initially, the expression of lncRNA-LUADT1 and TEAD1 were significantly up-regulated in NPC tissues and cells, while miR-1207-5p was significantly down-regulated. Next, miR-1207-5p was confirmed to bind to lncRNA-LUADT1 or TEAD1 by bioinformatics and luciferase reporter assay. In addition, after interfering with lncRNA-LUADT1 expression, experiments of CCK8, EDU staining, and Transwell invasion were used to detect proliferation, invasion, and migration of NPC cells. The results showed that interfering with lncRNA-LUADT1 expression could inhibit the proliferation, invasion, and migration of NPC cells. Western blot showed that lncRNA-LUADT1 knockdown significantly decreased the expression of Hippo/YAP pathway protein (YAP1 and TAZ). However, interfering with the expression of miR-1207-5p reversed these results. In addition, the nude mouse tumor formation experiment suggested that low-expressed lncRNA-LUADT1 reduced the volume and weight of tumor tissues. In summary, lncRNA-LUADT1 down-regulation could inhibit NPC cell proliferation and invasion, which may be achieved through regulating miR-1207-5p expression and affecting TEAD1 expression, thus inhibiting the activation of Hippo/YAP signaling pathway.

LncRNA-PVT1 indicates a poor prognosis and promotes angiogenesis via activating the HNF1B/EMT axis in glioma.

Recent studies identified that long non-coding RNAs (lncRNAs) exhibited critical roles in tumor migration and invasion. However, the roles of lncRNAs in glioma remain unclear. The aim of this study was to uncover the underlying mechanisms of glioma progression and provide potential therapeutic targets for its treatment in clinic. Our microarray study showed that lncRNA-PVT1 was significantly upregulated in glioma tissues and played an important role in cell proliferation, migration, invasion and angiogenesis. Our data showed that the expression of lncRNA-PVT1 was increased obviously and associated with advanced tumor stage, metastasis, invasion ability, and poor prognosis in glioma patients. Up-regulation of lncRNA-PVT1 was observed to promote glioma cells proliferation, and invasion abilities in vitro as well as tumor growth in vivo by regulating miR-1207-3p expression. Online software (TargetScan, miRDB and miR TarBase) were used to predict the regulating mechanisms of lncRNA-PVT1, miR-1207-3p and HNF1B, which were validated by dual-luciferase reporter gene system. In vivo tumor-bearing mice models were established to validate the cellular results. Therefore, we suggested that lncRNA-PVT1/miR-1207-3p/HNF1B axis might play critical roles in glioma progression, indicating that lncRNA-PVT1/miR-1207-3p/HNF1B signaling axis may serve as novel molecular targets for glioma prevention and treatment.

miR-1207-5p suppresses laryngeal squamous cell carcinoma progression by downregulating SKA3 and inhibiting epithelial-mesenchymal transition.

Laryngeal squamous cell carcinoma (LSCC) is the second most common head and neck cancer. Previously, we discovered that miR-1207-5p was downregulated in LSCC. In this study, the clinical significance, function, and mechanism of miR-1207-5p in LSCC were investigated. Downregulation of miR-1207-5p was found to be strongly linked to the malignant progression of LSCC. Functional studies revealed that miR-1207-5p upregulation suppressed LSCC cell proliferation, invasion, migration, and xenograft tumor growth. Bioinformatics analysis revealed that miR-1207-5p target genes were involved in cell cycle regulation, proliferation, adhesion, and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Mechanistic studies revealed that miR-1207-5p interacts directly with the 3' untranslated region of spindle and kinetochore associated complex subunit 3 (SKA3) and downregulates SKA3 expression. Furthermore, SKA3 was found to be overexpressed in LSCC, and its high expression was associated with tumor progression and a poor prognosis. Rescue experiments demonstrated that miR-1207-5p inhibited the malignant phenotypes of LSCC via SKA3. Furthermore, miR-1207-5p upregulation or knockdown of SKA3 inhibited the epithelial-mesenchymal transition (EMT). Collectively, miR-1207-5p inhibited LSCC malignant progression by downregulating SKA3 and preventing EMT. These findings provide new insights into the mechanism of LSCC progression, as well as new potential biomarkers and therapeutic targets for LSCC diagnosis and treatment.

MiR-1207-5p targets PYCR1 to inhibit the progression of prostate cancer.

Prostate cancer, the most common non-cutaneous male cancer, is a public health problem with a third prevalence worldwide. PYCR1 and miR-1207-5p dysregulations were found in cancer progression. Our study aims to reveal the biological role of miR-1207-5p-PYCR1 axis in prostate cancer progression. First, we investigated the expression of miR-1207-5p in prostate cancer tissues and cell lines by RT-qPCR. Next, we confirmed miR-1207-5p targeting PYCR1 by luciferase assay. CCK-8 assay, BrdU assay, flow cytometry, and tanswell assay were applied for examining cell proliferation, apoptosis, and invasion in prostate cancer cells, respectively. In the present study, decreased miR-1207-5p expression was obviously observed in prostate cancer tissues and cells. Upregulation of miR-1207-5p hampered cellular proliferation and invasion, while enhanced cellular apoptosis. In addition, upregulation of PYCR1 elevated cell proliferation and invasion, but repressed apoptosis of prostate cancer cells. Moreover, miR-1207-5p inhibited the expression of PYCR1 to repress prostate cancer tumorigenesis. MiR-1207-5p inhibited the expression of PYCR1 to repress the progression of prostate cancer by inhibiting cell growth and elevating cell apoptosis. Overall, our study clarifies the biological role of miR-1207-5p-PYCR1 axis in prostate cancer progression, which might be effective biomarkers for clinical treatment of prostate cancer.

LncRNA MIR194-2HG Promotes Cell Proliferation and Metastasis via Regulation of miR-1207-5p/TCF19/Wnt/ß-Catenin Signaling in Liver Cancer.

PURPOSE: LncRNAs play an important role in tumorigenesis and cancer progression in liver cancer. Although many lncRNAs have been reported, the role of MIR194-2HG and the underlying mechanism mediated by it are still largely unknown in HCC. This study aimed to investigate the biological role and mechanism of MIR194-2HG in liver cancer. MATERIALS AND METHODS: The expression of MIR194-2HG was determined in liver cancer tissues and cells by RT-qPCR. The overall survival rate of MIR194-2HG was analyzed by Kaplan-Meier survival analysis. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and Transwell assays were carried out to detect cell migration and invasion. Western blotting was used to quantify the levels of all proteins. The regulatory mechanism of the MIR194-2HG/miR-1207-5p/TCF19 axis in liver cancer was investigated by dual-luciferase activity reporter assay, Kaplan-Meier survival analysis, and Western blotting. RESULTS: MIR194-2HG was upregulated in liver cancer tissues and cell lines. Liver cancer patients with higher expression of MIR194-2HG revealed poor overall survival compared with those who had lower expression of MIR194-2HG. MIR194-2HG promoted the proliferation, migration, and invasion of HepG2 and Huh7 cells by acting as a ceRNA mechanism for the miR-1207-5p/TCF19 axis to activate the Wnt/ß-catenin signaling pathway. CONCLUSION: MIR194-2HG acts in an oncogenic role and activates the Wnt/ß-catenin signaling pathway via a miR-1207-5p/TCF19 axis-mediated mechanism, which provides a novel avenue for diagnostic or therapeutic interventions in liver cancer.

MiR-1207-5p/CX3CR1 axis regulates the progression of osteoarthritis via the modulation of the activity of NF-κB pathway.

BACKGROUND: Osteoarthritis (OA) is a prevalent chronic diseases characterized by formation of osteophytes and degradation of articular cartilage. Previous evidence has identified the regulatory effects of microRNAs (miRNAs) in OA. The goal of this study is to clearly explore the biological function of miR-1207-5p in OA. METHODS: MiR-1207-5p and C-X3-C motif chemokine receptor 1 (CX3CR1) expression in OA cartilages were revealed by accessing to Gene Expression Omnibus database. In vitro OA model was established by lipopolysaccharide (LPS) stimulation. Western blot and quantitative real-time polymerase chain reaction were conducted to detect the expression level of genes. Cell counting kit-8 (CCK-8) and flow cytometric experiments were performed to investigate the proliferation and apoptosis capacities of CHON-001 cells. Bioinformatics analysis was applied to predict the binding site of miR-1207-5p and CX3CR1, the connections of which were ascertained using luciferase reporter assay. RESULTS: MiR-1207-5p expression was decreased while CX3CR1 was increased in OA cartilages. Up-regulation of miR-1207-5p alleviated the LPS-induced damage in the view of cell proliferation, apoptosis and extracellular matrix (ECM) degradation. A target of miR-1207-5p CX3CR1, its down-regulation intensified the impacts of miR-1207-5p mimic, promoted proliferation and mitigated apoptosis. LPS exposure increased the protein expression of the phosphorylated IκBα and P65, and this phenomena was reversed due to miR-1207-5p up-regulation and CX3CR1 knockdown. The treatment of Betulinic acid (BA; an activator of nuclear factor-κB pathway) reversed the miR-1207-5p mimic-induced inhibitory effect on apoptosis in LPS-treated CHON-001. CONCLUSION: Our results highlight that miR-1207-5p can prevent CHON-001 from LPS-stimulated injury, providing a novel biomarker for OA progression and further advancing treatment of OA.

Characterization of antiapoptotic microRNAs in primary Sjögren's syndrome.

During the development of primary Sjögren's syndrome (pSS), aberrant expression of autoantigen is a hallmark event. To explore the regulation of autoantigen tripartite motif containing 21 (Ro/SSA, TRIM21), microRNA profiling was performed in our previous study. In which, two TRIM21-targeting microRNAs were identified, namely miR-1207-5p and miR-4695-3p. To further pursue their roles in the development of pSS, assays were performed with cultured human submandibular gland (HSG) cells, and salivary gland tissues. Results showed that transfection of miR-1207-5p or miR-4695-3p mimics down-regulated not only the expression of TRIM21, but also the levels of pro-apoptotic genes B cell lymphoma 2 associated X (BAX), Caspase 9 (CASP-9) and Caspase 8 (CASP-8). This finally led to antiapoptotic phenotypes in HSG cells. Consistent with the antiapoptotic activity, transfection of microRNA inhibitors up-regulated the expression of TRIM21 and led to a pro-apoptotic phenotype. These therefore propose miR-1207-5p and miR-4695-3p as two antiapoptotic microRNAs functioning through apoptosis pathway. Supporting this speculation, assays performed with salivary gland tissues revealed down-regulation of miR-1207-5p and miR-4695-3p, as well as up-regulation of TRIM21 and pro-apoptotic CASP-8 gene in pSS samples. SIGNIFICANCE OF THE STUDY: For pSS patients, apoptosis of acinar and ductal epithelial cells has been proposed to be a potential mechanism that impairs the secretion of salivary glands. In our study, two autoantigen-targeting microRNAs were characterized as antiapoptotic microRNAs functioning through apoptosis pathway, which may be potential targets for the treatment of pSS.

LncRNA OR3A4 Regulated the Growth of Osteosarcoma Cells by Modulating the miR-1207-5p/G6PD Signaling.

BACKGROUND: Increasing evidence has demonstrated the importance of non-coding RNAs including long non-coding RNA (lncRNA) and microRNAs (miRNAs) in the tumorigenesis of osteosarcoma (OS). Abnormal expression of lncRNA olfactory receptor family 3 subfamily A member 4 (OR3A4) was found in multiple human cancers; however, the function of OR3A4 in OS remains largely unknown. MATERIALS AND METHODS: The expression level of OR3A4 in OS tissues and cell lines was detected by RT-qPCR. Cell counting kit-8 assay, colony formation and flow cytometry analysis were performed to determine the growth of OS cells. The targets of OR3A4 were predicted using the miRDB database. The binding between OR3A4 and miRNAs was confirmed by dual-luciferase reporter assay. RESULTS: OR3A4 was overexpressed in OS tissues and correlated with the advanced progression of OS patients. Down-regulation of OR3A4 significantly inhibited the proliferation and colony formation of OS cells. Mechanistically, OR3A4 acted as a sponge of miR-1207-5p. Glucose-6-phosphate dehydrogenase (G6PD) was identified as a target of miR-1207-5p. Knockdown of OR3A4 increased the expression of miR-1207-5p and consequently, suppressed the level of G6PD in OS cells. Due to the essential role of G6PD in the pentose phosphate pathway (PPP), depletion of OR3A4 inhibited NADPH production, glucose consumption and lactate generation. Decreased level of NADPH by depletion of OR3A4 up-regulated the redox state (ROS) content and resulted in endoplasmic reticulum (ER) stress in OS cells. Restoration of G6PD significantly attenuated the cell growth inhibition induced by OR3A4 knockdown. CONCLUSION: Our finding suggested the critical role of OR3A4 in the proliferation of OS cells via targeting the miR-1207-5p/G6PD axis.

CircHIPK3 promotes colorectal cancer cells proliferation and metastasis via modulating of miR-1207-5p/FMNL2 signal.

Increasing evidences demonstrate that circular RNAs (circRNAs) are extensively implicated in various cancers including colorectal cancer (CRC). In the present study, we found that circRNA HIPK3 (circPIK3) was upregulated in CRC. We identified that circHIPK3 was closely related with unfavorable clinicopathological features in patients with CRC. Functional transwell assay and proliferation assay indicated that circHIPK3 served as an oncogene and promoted CRC cells migration, invasion and proliferation. Meanwhile, we found that formin like 2 (FMNL2) was a key downstream molecule in circHIPK3-induced metastasis and proliferation in CRC cells. We further verified that circHIPK3 was mainly located at cytoplasm through an immunofluorescence assay. An online bioinformatics screening and a GEO datasets analysis showed that microRNA 1207-5p (miR-1207-5p) was downregulated in CRC. Also, we found that miR-1207-5p shared a similar miR-1207-5p response elements (MREs-1207-5p). Meanwhile, we showed that miR-1207-5p suppressed CRC cells migration, invasion and proliferation via directly targeting of FMNL2. Even further, via a constructed luciferase assay, we indicated that circHIPK3 was another target of miR-1207-5p. Functionally, we proved that circHIPK3 enhanced FMNL2 mediated promotion of migration, invasion and proliferation by sponging of miR-1207-5p in CRC cells. In summary, the outcomes of this study illustrated that circHIPK3 promoted CRC cells migration, invasion and proliferation modulating of FMNL2 by sponging of miR-1207-5p. Our findings indicated that circHIPK3/miR-1207-5p/FMNL2 axis might be a new strategy in molecular treatment of CRC.

Tanshinol inhibits growth of malignant melanoma cells via regulating miR-1207-5p/CHPF pathway.

Tanshinol possesses anti-tumor activity in melanoma both in vitro and in vivo, and miR-1207-5p is involved in tumor progression in melanoma. However, whether miR-1207-5p can be affected by tanshinol treatment in melanoma is not clear. The expression levels of miR-1207-5p were detected by RT-qPCR. The validation of the direct target of miR-1207-5p was through dual-luciferase reporter assay and western blotting assay. The cell viability rate was determined using MTT assay and colony formation assay. The cell mobility was assessed using Transwell migration/invasion assay. Downregulation of miR-1207-5p was found in melanoma cell lines and tissues and was associated with tumor stages, presence of ulceration, lymph node metastasis, and poor overall survival rate of melanoma patients. Tanshinol treatment and miR-1207-5p overexpression suppressed melanoma cell growth and cell mobility. Chondroitin polymerizing factor (CHPF) is a direct target of miR-1207-5p. Tanshinol exerted anti-tumor activity to melanoma through the regulation of miR-1207-5p/CHPF signaling. Our study highlighted the potential therapeutic application of tanshinol and miR-1207-5p as a supplement to enhance the effect of the traditional cancer treatment methods against melanoma.

Long non-coding RNA 319 facilitates nasopharyngeal carcinoma carcinogenesis through regulation of miR-1207-5p/KLF12 axis.

Long non-coding RNAs (lncRNAs) have been wildly verified to modulate multiple tumorigeneses, especially nasopharyngeal carcinoma (NPC). In present study, we aim to investigate the role of LINC00319 in the NPC carcinogenesis. It was indicated that LINC00319 was markedly increased in NPC tissues and cells in comparison to their corresponding controls. Moreover, the aberrant overexpression of LINC00319 indicated the poor prognosis of NPC patients. Silence of LINC00319 was able to suppress NPC cell growth in vitro while overexpression of LINC00319 inversed this process. Moreover, in vivo tumor xenografts were established using CNE-1/SUNE-1 cells to investigate the function of LINC00319 in NSCLC tumorigenesis. Rescue assay was performed to further confirm that LINC00319 contributed to NPC progression by regulating miR-1207-5p/KLF12 signal pathway. Taken together, our study discovered the oncogenic role of LINC00319 in clinical specimens and cellular experiments, showing the potential LINC00319/miR-1207-5p/KLF12 pathway. This results and findings provide a novel insight for NPC tumorigenesis.

Non-Coding RNA Pvt1 Promotes Cancer Stem Cell-Like Traits in Nasopharyngeal Cancer via Inhibiting miR-1207.

Nasopharyngeal carcinoma (NPC) is a kind of head-neck malignant tumor. lncRNA-PVT1 can promote the proliferation of carcinoma cells, and induce cells to have stem cell-like potentials. However, the function of PVT1 in NPC cells is not clear. The expressions of lncRNA-PVT1 and the expressions of the stem cell markers in NPC tissues or cell lines were investigated by qRT-PCR or western blot. The cell proliferation, and the ability of NPC cells to form spherical, clonal colonies were investigated by MTT assay, colony formation assay, and tumor-sphere formation assay. Cancer stem cells surface markers were detected by flow cytometry and western blot. PI3K/AKT signal activation in NPC cells was determined by western blot. PVT1 was significantly up-regulated in both NPC tissues and cell lines and associated with poor prognosis. PVT1 knockdown reduced NPC cells viability, clonogenicity, the cell surface CD44+/CD24- stem phenotype, and the expressions of the stem cell markers in NPC cells, including Oct4, c-Myc, SOX2, and ALDH. Furthermore, PVT1 negatively regulates the expression levels of miR-1207 in NPC cells and spheres cells, which is critical for NPC stemness. Knockdown of miR-1207 promoted stem phenotype and the expressions of the stem cell markers in NPC cells. Moreover, phosphor-PI3K (p-PI3K) and phosphor-AKT (p-AKT) were found to be down-regulated after PVT1 siRNAs transfection in NPC cells. And miR-1207 inhibitor transfection reversed the all the effects brought by PVT1 knockdown. Pvt1 promotes cancer stem cell-like properties in NPC cells via inhibiting miR-1207 and activating the PI3K/AKT signal pathway.

Upregulation of LINC00319 indicates a poor prognosis and promotes cell proliferation and invasion in cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (CSCC), an epidermal keratinocyte-derived skin tumor, is one of the most leading causes of cancer-associated morbidity and mortality worldwide. Long noncoding RNAs have emerged as key regulators of tumor development and progression. Recent studies have identified LINC00319, a long intergenic noncoding RNA, as an oncogene in lung cancer. However, the biological role of LINC00319 in CSCC remains largely unknown. The current study aimed to explore the role of LINC00319 in CSCC and uncover the molecular mechanisms. In current study, we found that LINC00319 was significantly upregulated in both CSCC tissues and cell lines. Besides, the χ2 test showed that increased expression of LINC00319 was associated with larger tumor size, advanced TNM stage, and lymphovascular invasion. Gain-of-function and loss-of-function approaches were applied to investigate the effects of LINC00319 on CSCC cells. Functional studies demonstrated that LINC00319 promoted CSCC cell proliferation, accelerated cell cycle progression, facilitated cell migration and invasion, and inhibited cell apoptosis. Mechanistic studies revealed that LINC00319 exerts its oncogenic functions in CSCC via miR-1207-5p-mediated regulation of cyclin-dependent kinase 3. Taken together, upregulation of LINC00319 implies a potential link with poor prognosis and reflects CSCC progression. Collectively, this study may provide some evidence for LINC00319 as a candidate target in CSCC treatment.

A novel microRNA-1207-3p/FNDC1/FN1/AR regulatory pathway in prostate cancer.

Prostate cancer (PCa) is the second most common cause of cancer-specific deaths in the U.S. Unfortunately, the underlying molecular mechanisms for its development and progression remain unclear. Studies have established that microRNAs (miRNAs) are dysregulated in PCa. The intron-derived microRNA-1207-3p (miR-1207-3p) is encoded at the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, miR-1207-3p in PCa had not previously been investigated. Therefore, we explored if miR-1207-3p plays any regulatory role in PCa. We discovered that miR-1207-3p is significantly underexpressed in PCa cell lines in comparison to normal prostate epithelial cells, and that increased expression of microRNA-1207-3p in PCa cells significantly inhibits proliferation, migration, and induces apoptosis via direct molecular targeting of fibronectin type III domain containing 1 (FNDC1). Our studies also revealed significant overexpression of FNDC1, fibronectin (FN1) and the androgen receptor (AR) in human PCa cell lines as well as tissues, and FNDC1, FN1, and AR positively correlate with aggressive PCa. These findings, recently published in Experimental Cell Research, are the first to describe a novel miR-1207-3p/FNDC1/FN1/AR novel regulatory pathway in PCa.

PVT1-derived miR-1207-5p promotes breast cancer cell growth by targeting STAT6.

Accumulating evidence indicates that ectopic expression of non-coding RNAs are responsible for breast cancer progression. Increased non-coding RNA PVT1, the host gene of microRNA-1207-5p (miR-1207-5p), has been associated with breast cancer proliferation. However, how PVT1 functions in breast cancer is still not clear. In this study, we show a PVT1-derived microRNA, miR-1207-5p, that promotes the proliferation of breast cancer cells by directly regulating STAT6. We first confirm the positive correlated expression pattern between PVT1 and miR-1207-5p by observing consistent induced expression by estrogen, and overexpression in breast cancer cell lines and breast cancer patient specimens. Moreover, silence of PVT1 also decreased miR-1207-5p expression. Furthermore, increased miR-1207-5p expression promoted, while decreased miR-1207-5p expression suppressed, cell proliferation, colony formation, and cell cycle progression in breast cancer cell lines. Mechanistically, a novel target of miR-1207-5p, STAT6, was identified by a luciferase reporter assay. Overexpression of miR-1207-5p decreased the levels of STAT6, which activated CDKN1A and CDKN1B to regulate the cell cycle. We also confirmed the reverse correlation of miR-1207-5p and STAT6 expression levels in breast cancer samples. Therefore, our findings reveal that PVT1-derived miR-1207-5p promotes the proliferation of breast cancer cells by targeting STAT6, which in turn controls CDKN1A and CDKN1B expression. These findings suggest miR-1207-5p might be a potential target for breast cancer therapy.

miR-1207-3p regulates the androgen receptor in prostate cancer via FNDC1/fibronectin.

Prostate cancer (PCa) is frequently diagnosed in men, and dysregulation of microRNAs is characteristic of many cancers. MicroRNA-1207-3p is encoded at the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of microRNA-1207-3p in PCa is unclear. We discovered that microRNA-1207-3p is significantly underexpressed in PCa cell lines in comparison to normal prostate epithelial cells. Increased expression of microRNA-1207-3p in PCa cells significantly inhibits proliferation, migration, and induces apoptosis via direct molecular targeting of FNDC1, a protein which contains a conserved protein domain of fibronectin (FN1). FNDC1, FN1, and the androgen receptor (AR) are significantly overexpressed in PCa cell lines and human PCa, and positively correlate with aggressive PCa. Prostate tumor FN1 expression in patients that experienced PCa-specific death is significantly higher than in patients that remained alive. Furthermore, FNDC1, FN1 and AR are concomitantly overexpressed in metastatic PCa. Consequently, these studies have revealed a novel microRNA-1207-3p/FNDC1/FN1/AR regulatory pathway in PCa.

The effects of miR-1207-5p expression in peripheral blood on cisplatin-based chemosensitivity of primary gallbladder carcinoma.

OBJECTIVE: The aim of this study was to investigate the association between miR-1207-5p expression in peripheral blood and the chemosensitivity of primary gallbladder carcinoma (PGBC). METHODS: A total of 85 patients with PGBC undergoing preoperative chemotherapy were divided into effective (n=18) and ineffective (n=67) groups. Another 70 healthy individuals were selected as the control group. An miR-1207-5p mimic (mimic group), an inhibitor (inhibitor group), and a negative control (NC group) sequence were transfected into human gallbladder carcinoma GBC-SD cells. Real-time quantitative polymerase chain reaction was used to determine miR-1207-5p expression. After 48 hours of cisplatin treatment, CCK-8 method was used to detect cell proliferation and flow cytometry were performed to examine cell apoptosis. RESULTS: miR-1207-5p expression in peripheral blood was significantly associated with tumor node metastasis staging of PGBC (P<0.05). Before chemotherapy, miR-1207-5p expression in patients was higher than in healthy individuals (P<0.05). After chemotherapy, the effective group had lower miR-1207-5p expression than the ineffective group (P<0.05). The rates of positive expression of Ki67 protein in the effective group were significantly lower than those in the ineffective group (P<0.05). Receiver operating characteristic curves showed that the area under curve, sensitivity, and specificity of miR-1207-5p used to diagnose PGBC were 0.898, 77.6%, and 97.1% at a cutoff of 1.470, respectively. After 48 hours of cisplatin treatment, compared with the NC group and nontransfected (non-T) group, the mimic group had decreased rates of cell inhibition and apoptosis, but the inhibitor group had increased rates (all P<0.05). The expression levels of caspase3 protein were increased in the mimic group and decreased in the inhibitor group. Cell survival rates in the mimic group at different time points after cisplatin treatment were significantly higher than the corresponding rates in the NC and non-T groups, whereas the cell survival rates in the inhibitor group were significantly lower than the rates in the NC and non-T groups (all P<0.05). The concentration and action time of cisplatin were negatively associated with the cell survival rate in each group (all P<0.05). CONCLUSION: Cisplatin-based chemosensitivity of PGBC increased as expression of miR-1207-5p in peripheral blood declined. Thus, miR-1207-5p appears to be a promising and novel chemosensitizer for the treatment of PGBC.