Ame-miR-1-3p of bee venom reduced cell viability through the AZIN1/OAZ1-ODC1-polyamines pathway and enhanced the defense ability of honeybee (Apis mellifera L.).

Bee venom serves as an essential defensive weapon for bees and also finds application as a medicinal drug. MicroRNAs (miRNAs) serve as critical regulators and have been demonstrated to perform a variety of biological functions. However, the presence of miRNAs in bee venom needs to be confirmed. Therefore, we conducted small RNA sequencing and identified 158 known miRNAs, 15 conserved miRNAs and 4 novel miRNAs. It is noteworthy that ame-miR-1-3p, the most abundant among them, accounted for over a quarter of all miRNA reads. To validate the function of ame-miR-1-3p, we screened 28 candidate target genes using transcriptome sequencing and three target gene prediction software (miRanda, PITA and TargetScan) for ame-miR-1-3p. Subsequently, we employed real-time quantitative reverse transcription PCR (qRT-PCR), Western blot and other technologies to confirm that ame-miR-1-3p inhibits the relative expression of antizyme inhibitor 1 (AZIN1) by targeting the 3' untranslated region (UTR) of AZIN1. This, in turn, caused ODC antizyme 1 (OAZ1) to bind to ornithine decarboxylase 1 (ODC1) and mark ODC1 for proteolytic destruction. The reduction in functional ODC1 ultimately resulted in a decrease in polyamine biosynthesis. Furthermore, we determined that ame-miR-1-3p accelerates cell death through the AZIN1/OAZ1-ODC1-polyamines pathway. Our studies demonstrate that ame-miR-1-3p diminishes cell viability and it may collaborate with sPLA2 to enhance the defence capabilities of honeybees (Apis mellifera L.). Collectively, these data further elucidate the defence mechanism of bee venom and expand the potential applications of bee venom in medical treatment.

Identification of key miRNAs in unilateral mastication-induced disruption of cartilage homeostasis.

OBJECTIVE: The present study identified potentially pivotal miRNAs contributing to chondrogenic differentiation in temporomandibular joint suffering abnormal stress. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into control and experimental unilateral mastication (EUM) group. Bone micro-structure parameters was detected by micro-CT, and FGF-1 and MMP-1 expression was examined by immunohistochemistry. Differentially expressed miRNAs of bilateral condyle cartilage were screened via miRNA microarray at 4- and 8-week EUM, then further verified using quantitative reverse-transcription PCR. Over-expression of five differentially expressed miRNAs in chondrocytes was triggered by transfecting miRNA mimics. The expression of MMP-13, Col-II, OPN, and Runx2 was verified by western blotting. RESULTS: Expressions of FGF-1 and MMP-1 in right condyles gradually increased from 2 to 6 weeks after EUM. A total of 20 differentially expressed miRNAs were regulated by EUM, which related to cell proliferation, invasion, and osteoblast differentiation pathways. The over-expression of miR-148a-3p and miR-1-3p led to down-regulation of Col-II, while MMP-13 and Runx2 were up-regulated by induction of hypotrophic differentiation or IL-1ß stimulation. These findings suggested that miR-148a-3p and miR-1-3p promote chondrogenic differentiation. CONCLUSIONS: Several pivotal miRNAs were found to be related to chondrogenic differentiation, which provides novel insight into pathogenic mechanisms of cartilage homeostasis.

The important role of miR-1-3p in cancers.

Cancer is a malignant tumor that seriously threatens human life and health. At present, the main treatment methods include surgical resection, chemotherapy, radiotherapy, and immunotherapy. However, the mechanism of tumor occurrence and development is complex, and it produces resistance to some traditional treatment methods, leading to treatment failure and a high mortality rate for patients. Therefore, exploring the molecular mechanisms of tumor occurrence, development, and drug resistance is a very important task. MiRNAs are a type of non-coding small RNA that regulate a series of biological effects by binding to the 3'-UTR of the target mRNA, degrading the mRNA, or inhibiting its translation. MiR-1-3p is an important member of them, which is abnormally expressed in various tumors and closely related to the occurrence and development of tumors. This article introduces miR-1-3p from multiple aspects, including its production and regulation, role in tumor occurrence and development, clinical significance, role in drug resistance, and approaches for targeting miR-1-3p. Intended to provide readers with a comprehensive understanding of the important role of miR-1-3p in tumors.

MALAT1/ mir-1-3p mediated BRF2 expression promotes HCC progression via inhibiting the LKB1/AMPK signaling pathway.

BACKGROUND: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to play a vital role in the occurrence and development of various tumors. However, the underlying mechanism of MALAT1 in hepatocellular carcinoma (HCC) has not been thoroughly elucidated. METHODS: The expression levels of MALAT1 in HCC tissues and different cell lines were detected by qRT-PCR. Antisense oligonucleotides (ASO)-MALAT1 transfected cells were used to explore the biological effects of MALAT1 in HCC cells by cell counting kit 8 (CCK-8), colony formation, transwell, wound healing, and flow cytometry analysis. Western blotting was performed to measure AMPK and apoptosis-related protein levels. Dual-luciferase reporter assay was performed to verify the relationship between MALAT1 and its specific targets. RESULTS: We found that MALAT1 was upregulated in HCC, and MALAT1 knockdown in HCC cells inhibited cell proliferation, migration, and invasion and inhibited apoptosis in vitro. Further studies demonstrated that MALAT1 positively regulated the expression of transcription factor II B­related factor 2 (BRF2), which was associated with tumor recurrence, large tumor size, and poor prognosis in HCC. Mechanistically, MALAT1 was found to act as a competitive endogenous RNA to sponge has-miR-1-3p, which upregulated BRF2 expression. Knockdown of BRF2 inhibited the progression of HCC by activating the LKB1/AMPK signaling pathway. Overexpression of BRF2 reversed the inhibitory effect of MALAT1 knockdown on HCC cell viability. Moreover, ASO targeting MALAT1 inhibited the growth of xenograft tumors. CONCLUSIONS: Our results demonstrate a novel MALAT1/miR-1-3p/BRF2/LKB1/AMPK regulatory axis in HCC, which may provide new molecular therapeutic targets for HCC in the future.

MiR-1-3p targets CENPF to repress tumor-relevant functions of gastric cancer cells.

Here we noted significantly downregulated miR-1-3p in gastric cancer (GC) tissue compared with adjacent normal tissue through qRT-PCR. Lowly expressed miR-1-3p correlated GC progression. Overexpressing miR-1-3p could restrain tumor-relevant cell behaviors in GC, while miR-1-3p inhibitor treatment triggered the opposite results. Moreover, dual-luciferase reporter gene detection identified specific binding sites of miR-1-3p in CENPF 3'untranslated region. Upregulating miR-1-3p constrained cell progression of GC via CENPF downregulation. Western blot, qRT-PCR and dual-luciferase detections manifested that miR-1-3p negatively mediated CENPF expression in GC cells. Thus, we demonstrated that miR-1-3p negatively mediated CENPF to hamper GC progression. CENPF may be an underlying target for GC therapy.

A novel ceRNA-immunoregulatory axis based on immune cell infiltration in ulcerative colitis-associated colorectal carcinoma by integrated weighted gene co-expression network analysis.

BACKGROUND: Patients with ulcerative colitis are at an increased risk of developing colorectal cancer with a prolonged disease course. Many studies have shown that alterations in the immune microenvironment play a key role in ulcerative colitis-associated colorectal cancer. Additionally, competing endogenous RNAs have important functions in immunoregulation, affecting inflammation and tumorigenesis. However, the complexity and behavioral characteristics of the competing endogenous RNA immunoregulatory network in ulcerative colitis-associated colorectal cancer remain unclear. We constructed a competing endogenous RNA immunoregulatory network to discover and validate a novel competing endogenous RNA immunoregulatory axis to provide insight into ulcerative colitis-associated colorectal cancer progression. METHODS: The competing endogenous RNA immunoregulatory network was constructed using differential expression analysis, weighted gene co-expression network analysis, and immune-related genes. Cmap was used to identify small-molecule drugs with therapeutic potential in ulcerative colitis-associated colorectal cancer. The ulcerative colitis-associated colorectal cancer-related pathways were identified by gene set variation and enrichment analysis. CIBERSORT, single-sample Gene Set Enrichment Analysis, and xCell were used to evaluate the infiltration of immune cells and screen hub immunocytes. The competing endogenous RNA immunoregulatory axis was identified by correlation analysis. RESULTS: We identified 130 hub immune genes and constructed a competing endogenous RNA immunoregulatory network consisting of 56 long non-coding RNAs, four microRNAs, and six targeted hub immune genes. Four small-molecule drugs exerted potential therapeutic effects by reversing the expression of hub immune genes. Pathway analysis showed that the NF-κB pathway was significantly enriched. Neutrophils were identified as hub immunocytes, and IL6ST was significantly positively correlated with the neutrophil count. In addition, NEAT1 may serve as a competing endogenous RNA to sponge miR-1-3p and promote IL6ST expression. CONCLUSIONS: The competing endogenous RNA immunoregulatory axis may regulate neutrophil infiltration, affecting the occurrence of ulcerative colitis-associated colorectal cancer.

LncRNA TUG1 functions as a ceRNA for miR-1-3p to promote cell proliferation in hepatic carcinogenesis.

BACKGROUND: Hepatocellular carcinoma (HCC) is characterised by high malignancy, metastasis and recurrence, but the specific mechanism that drives these outcomes is unclear. Recent studies have shown that long noncoding RNAs (lncRNAs) can regulate the proliferation and apoptosis of hepatic cells. METHODS: We searched for lncRNAs and microRNAs (miRNAs), which can regulate IGF1 expression, through a bioinformatics website, and predicted that lncRNA taurine-upregulated gene 1 (TUG1) would have multiple targets for miR-1-3p binding, meaning that lncRNA TUG1 played an adsorption role. A double luciferase assay was used to verify the targeting relationship between lncRNA TUG1 and miR-1-3p. Western blotting and qPCR were used to verify the targeting relationship between miR-1-3p and IGF1, and qPCR was used to verify the regulatory relationship between the lncRNA TUG1-miR-1-3p-IGF1 axis. CCK-8 was used to detect the growth activity of miRNA-transfected L-O2 cells, and flow cytometry was used to detect cell cycle changes and apoptosis. RESULT: The proliferation cycle of L-O2 cells transfected with miR-1-3p mimics was significantly slowed. Flow cytometry showed that the proliferation of L-O2 cells was slowed, and the apoptosis rate was increased. In contrast, when L-O2 cells were transfected with miR-1-3p inhibitor, the expression of IGF1 was significantly upregulated, and the cell proliferation cycle was significantly accelerated. Flow cytometry showed that the cell proliferation rate was accelerated, and the apoptosis rate was reduced. CONCLUSION: LncRNA TUG1 can adsorb miR-1-3p as a competitive endogenous RNA (ceRNA) to promote the expression of IGF1 and promote cell proliferation in hepatic carcinogenesis.

LncRNA H19 Regulates Proliferation, Apoptosis and ECM Degradation of Aortic Smooth Muscle Cells Via miR-1-3p/ADAM10 Axis in Thoracic Aortic Aneurysm.

Thoracic aortic aneurysm (TAA) is a prevalent health problem worldwide. Long non-coding RNA H19was highly expressed in TAA patients, but the function and mechanism of H19 in TAA remain unknown. The expression levels of H19, microRNA-1-3p (miR-1-3p), and a disintegrin and metalloproteinase 10 (ADAM10) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROS) cure was performed to evaluate the diagnostic value of H19 on TAA patients. Proliferation and apoptosis were detected by Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry. Protein levels of proliferating cell nuclear antigen (PCNA), Cleaved-caspase 3 (Cleaved-cas3), Cleaved-caspase 9 (Cleaved-cas9), Collagen I, Collagen III, and ADAM10 were tested by western blot assay. The binding relationship between miR-1-3p and H19 or ADAM10 was predicted by LncBase Predicted v.2 or Starbase, and verified by the dual-luciferase reporter, RNA pull-down assay, and RNA Immunoprecipitation (RIP) assays. H19 was increased in TAA aorta tissues and serum and vascular smooth muscle cell (VSMC), and hindered proliferation as well as promoted apoptosis and extracellular matrix (ECM) degradation of VSMC. Moreover, miR-1-3p was decreased, and ADAM10 was upregulated in TAA aorta tissues and VSMC. The mechanical analysis confirmed that H19 affected ADAM10 expression by targeting miR-1-3p. Our results indicated that H19 inhibited proliferation, and accelerated apoptosis and ECM degradation of VSMC, providing an underlying lncRNA-targeted therapy for TAA treatment.

Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3p.

Hepatocellular carcinoma (HCC) is characterized by its high vascularity and metastasis. Thymoquinone (TQ), the main bio-active constituent of Nigella sativa, has shown anticancer and hepatoprotective effects. TQ's anticancer effect is mediated through miRNA regulation. miR-1-3p plays a significant role in various cancers but its role in HCC invasiveness remains poorly understood. Bio-informatics analysis predicted that the 3'-UTR of TIMP3 is a target for miR-1-3p; Rats were equally divided into four groups: Group 1, the negative control; Group 2 received TQ; Group 3 received DEN; and Group 4 received DEN after pretreatment with TQ. The expression of TIMP3, MMP2, MMP9, and VEGF in rats' liver was determined immunohistochemically. RT-qPCR was used to measure the miR-1-3p level in rats' liver, and TIMP3, MMP2, MMP9, and VEGF in the HepG2 cells after being transfected with miR-1-3p mimic or inhibitor; In rats pretreated with TQ, a decreased expression of MMP2, MMP9 and VEGF, and increased expression levels of TIMP3 and miR-1-3p were detected. Treating the HepG2 cells with miR-1-3p mimic led to the upregulation of TIMP3 and downregulation of MMP2, MMP9, and VEGF, and showed a significant delay in wound healing; These results suggested that the anti-angiogenic effect of TQ in HCC may be mediated through the regulation of miR-1-3p.

Circulating miRNA-1-3p as Biomarker of Accelerated Sarcopenia in Patients Diagnosed with Chronic Heart Failure.

Background: While sarcopenia is an important clinical finding in individuals diagnosed with chronic heart failure (CHF), efforts to identify a reliable biomarker capable of predicting the overall muscular and functional decline in CHF patients have been unsuccessful to date. Objectives: The objectives of this study were to study the diagnostic utility of MicroRNA (miRNA)-1-3p as a predictor of sarcopenia status in individuals diagnosed with CHF. Methods: In total, 80 individuals with heart failure exhibiting a left ventricular ejection fraction < 50% were enrolled in this study. All patients were analyzed to assess miR-1-3p expression levels, with body composition being evaluated through dual-energy X-ray absorptiometry and sarcopenia being defined based on the sum of appendicular lean muscle mass (ALM) divided by height in meters squared and handgrip strength (HGS). In addition, the activation of the Akt/mTOR signaling pathway was evaluated in these individuals. Results: In total, 40 of the enrolled patients (50%) exhibited sarcopenia. Sarcopenic patients presented with increased miR-1-3p expression levels as compared to non-sarcopenic individuals (1.69 ± 0.132 vs. 1.22 ± 0.106; p < 0.05). With respect to sarcopenic indices, appendicular skeletal mass index was most strongly correlated with miR-1-3p expression, which was also strongly correlated with HGS. High levels of Akt/mTOR signaling pathway components were expressed in sarcopenic individuals, highlighting a significant relationship between miR-1-3p activity and signaling through this pathway. Moreover, miR-1-3p was identified as a specific marker for sarcopenia in individuals with CHF. Conclusions: These results suggest that circulating miR-1-3p levels are related to Akt/mTOR pathway activation and can offer valuable insight into the overall physical capacity and muscular integrity of CHF patients as a predictor of sarcopenia. (Rev Invest Clin. 2022;74(5):276-83).

MiR-1-3p enhances the sensitivity of ovarian cancer cells to ferroptosis by targeting FZD7. / MiR-1-3p通过靶向FZD7增强卵巢癌细胞对铁死亡的敏感性.

OBJECTIVES: Frizzled 7 (FZD7) is abnormally expressed and activated in a variety of cancers. In ovarian cancer, overexpression of FZD7 reduces the sensitivity of platinum-resistant ovarian cancer cells to ferroptosis, thereby allowing cancer cells to survive. However, whether FZD7 inhibits ferroptosis in ovarian cancer cells and its mechanisms are remain unclear. This study aims to explore the effects of FZD7 and its upstream regulator miR-1-3p on ferroptosis in ovarian cancer cells are evaluated to clarify the molecular mechanism for miR-1-3p and FZD7's involvement in ferroptosis in ovarian cancer cells. METHODS: Human ovarian cancer cell lines HO8910 and SKOV3 were used as the research subjects. In the first part of the experiment, human ovarian cancer cells were transfected with blank plasmid and FZD7 overexpression plasmid, respectively; in the second and third parts, human ovarian cancer cells were transfected with miR-1-3p mimics negative control, miR-1-3p mimics, miR-1-3p inhibitors negative control, and miR-1-3p inhibitors, respectively; in the fourth part of the experiment, human ovarian cancer cells were transfected with miR-1-3p mimics and miR-1-3p mimics+FZD7 overexpression plasmid, respectively, and normal cultured cells were set as the control group. The human ovarian cancer cell ferroptosis model was established by incubating human ovarian cancer cells with different treatments with ferroptosis inducer Erastin or RSL3. Real-time RT-PCR was used to detect the mRNA expression levels of FZD7 and miR-1-3p; Western blotting was used to detect the protein expression levels of FZD7; CCK-8 assay was used to detect the cell viability; lipid peroxidation colorimetric assay kit was used to detect the level of intracellular MDA; and iron assay kit was used to detect the level of intracellular Fe2+. Dual-luciferase assay was used to detect the targeting relationship between miR-1-3p and FZD7. RESULTS: Overexpression of FZD7 increased the cell viability of human ovarian cancer cell lines HO8910 or SKOV3 (P<0.05, P<0.01, or P<0.001) and decreased the intracellular MDA levels (P<0.01) in Erastin-treated or RSL3-treated ovarian cancer cells. FZD7 was a direct target of miR-1-3p, which inhibited the expression of FZD7 (P<0.01) by binding to the 3'-untranslated region (3'UTR) site of FZD7. MiR-1-3p mimics decreased the cell viability of human ovarian cancer cell lines HO8910 or SKOV3 (P<0.05, P<0.01, or P<0.001) and increased the intracellular MDA levels (P<0.01) in Erastin-treated or RSL3-treated ovarian cancer cells; while miR-1-3p inhibitors significantly increased the cell viability of human ovarian cancer cell lines HO8910 or SKOV3 (P<0.05, P<0.01, or P<0.001) and decreased the intracellular MDA levels (P<0.01) in Erastin-treated or RSL3-treated ovarian cancer cells. The effect of miR-1-3p mimics on enhancing the sensitivity of human ovarian cancer cells to Erastin-induced or RSL3-induced ferroptosis was abrogated by overexpression of FZD7(P<0.05 or P<0.01). CONCLUSIONS: MiR-1-3p enhances the sensitivity of ovarian cancer cells to ferroptosis by targeting FZD7.

LINC00242/miR-1-3p/G6PD axis regulates Warburg effect and affects gastric cancer proliferation and apoptosis.

BACKGROUND: Reprogrammed glucose metabolism of enhanced Warburg effect (or aerobic glycolysis) is considered as a hallmark of cancer. Long non-coding RNAs (lncRNAs) have been certified to play a crucial role in tumor progression. The current study aims to inquire into the potential regulatory mechanism of long intergenic non-protein coding RNA 242 (LINC00242) on aerobic glycolysis in gastric cancer. METHOD: LINC00242, miR-1-3p and G6PD expression levels in gastric cancer tissues and cells were determined by qRT-PCR. Cell apoptosis or viability were examined by Flow cytometry or MTT assay. Western blot was utilized to investigate G6PD protein expression levels. Immunohistochemical (IHC) and hematoxylin and eosin (H&E) staining were used for histopathological detection. The targeted relationship between LINC00242 or G6PD and miR-1-3p was verified by luciferase reporter gene assay. Nude mouse xenograft was utilized to detect tumor formation in vivo. RESULT: LINC00242 and G6PD was high-expressed in gastric cancer tissues and cells, and LINC00242 is positively correlated with G6PD. Silencing of LINC00242 or G6PD within gastric cancer cells prominently inhibited cell proliferation and aerobic glycolysis in vitro and relieved the tumorigenesis of gastric cancer in vivo. miR-1-3p was predicted to directly target both LINC00242 and G6PD. Overexpression of miR-1-3p suppressed gastric cancer cells proliferation and aerobic glycolysis. LINC00242 competitively combined miR-1-3p, therefore relieving miR-1-3p-mediated suppression on G6PD. CONCLUSION: LINC00242 plays a stimulative role in gastric cancer aerobic glycolysis via regulation of miR-1-3p/ G6PD axis, therefore affecting gastric cancer cell proliferation.

Sepsis plasma-derived exosomal miR-1-3p induces endothelial cell dysfunction by targeting SERP1.

Acute lung injury (ALI) is the leading cause of death in sepsis patients. Exosomes participate in the occurrence and development of ALI by regulating endothelial cell inflammatory response, oxidative stress and apoptosis, causing serious pulmonary vascular leakage and interstitial edema. The current study investigated the effect of exosomal miRNAs on endothelial cells during sepsis. We found a significant increase in miR-1-3p expression in cecal ligation and puncture (CLP) rats exosomes sequencing and sepsis patients' exosomes, and lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) in vitro. However, the specific biological function of miR-1-3p in ALI remains unknown. Therefore, mimics or inhibitors of miR-1-3p were transfected to modulate its expression in HUVECs. Cell proliferation, apoptosis, contraction, permeability, and membrane injury were examined via cell counting kit-8 (CCK-8), flow cytometry, phalloidin staining, Transwell assay, lactate dehydrogenase (LDH) activity, and Western blotting. The miR-1-3p target gene was predicted with miRNA-related databases and validated by luciferase reporter. Target gene expression was blocked by siRNA to explore the underlying mechanisms. The results illustrated increased miR-1-3p and decreased stress-associated endoplasmic reticulum protein 1 (SERP1) expression both in vivo and in vitro. SERP1 was a direct target gene of miR-1-3p. Up-regulated miR-1-3p inhibits cell proliferation, promotes apoptosis and cytoskeleton contraction, increases monolayer endothelial cell permeability and membrane injury by targeting SERP1, which leads to dysfunction of endothelial cells and weakens vascular barrier function involved in the development of ALI. MiR-1-3p and SERP1 may be promising therapeutic candidates for sepsis-induced lung injury.

The LncRNA H19/miR-1-3p/CCL2 axis modulates lipopolysaccharide (LPS) stimulation-induced normal human astrocyte proliferation and activation.

Reactive astrocyte proliferation post SCI (spinal cord injury) leads to the formation of glial scars, thus hindering axon regeneration and SCI repair, during which the activation of astrocytes plays a central role. This study attempted to identify the lncRNA-miRNA-mRNA network which exerts a critical effect on normal human astrocyte (NHA) activation and proliferation during SCI inflammation. Herein, lncRNA H19 expression was increased by LPS in NHAs, and H19 was positively correlated with CCL2. H19 silencing in NHAs significantly attenuated the promoting effects of LPS stimulation on NHA proliferation and activation as manifested by inhibited cell viability and DNA synthesis capacity, reduced NHA activation markers, and reduced inflammatory factor concentrations (CCL2, IL-6, and TNF-α). miR-1-3p directly bound to H19 and the CCL2 3'UTR. miR-1-3p overexpression also attenuated the promoting effects of LPS stimulation on NHA proliferation and activation. H19 relieved miR-1-3p-induced inhibition of CCL2 expression by acting as a ceRNA. The inhibition of miR-1-3p could significantly reverse the effects of H19 silencing on NHA proliferation and activation, suggesting that the H19/miR-1-3p axis regulates the proliferation and activation of NHAs via CCL2. In conclusion, lncRNA H19, miR-1-3p, and CCL2 form a lncRNA-miRNA-mRNA axis that modulates NHA proliferation and activation in vitro.

Suppression of long non-coding RNA MALAT1 inhibits survival and metastasis of esophagus cancer cells by sponging miR-1-3p/CORO1C/TPM3 axis.

Esophageal cancer (EC) is a malignancy causing lots of mortality worldwide. Long non-coding RNAs (lncRNAs) are involved in the progression of multiple cancer types. The present study aimed to explore the function and associated mechanisms of lncRNA metastasis-associated lung adenocarcinoma transcript1 (MALAT1) in EC development by focusing on its interaction with miR-1-3p. The levels of MALAT1 and miR-1-3p were investigated in clinical EC specimens. Then, the expression of MALAT1 was knocked down in EC cell lines, and the effects of MALAT1 inhibition on the viability, migration, and invasion, and miR-1-3p/Coronin-1C (CORO1C)/Tropomyosin3 (TPM3) axis in EC cells were detected. The interaction between MALAT1 and miR-1-3p in the progression of EC was further determined by suppressing the expression of miR-1-3p in MALAT1 inhibition cells. The results were further verified with EC xenograft mice model. MALAT1 level was downregulated, while miR-1-3p level was upregulated in EC specimens. The inhibition of MALAT1 suppressed the viability, migration, and invasion in EC cell lines. The changes in phenotypes of EC cells were associated with the upregulation of miR-1-3p level and inhibition of CORO1C/TPM3 activity. Furthermore, the results of dual-luciferase assay showed the direct binding of MALAT1 to the seed sequence of miR-1-3p. The suppressed level of miR-1-3p not only induced the activity of CORO1C/TPM3 signaling, but also upregulated MALAT1 expression, indicating the reciprocal regulation between the two factors. The inhibition of MALAT1 also inhibited tumor growth and epithelial-mesenchymal transition (EMT) in mice model, which was reversed by miR-1-3p inhibition. Collectively, MALAT1 was important to the survival and metastasis of EC cells by sponging miR-1-3p.

MiR-21-5p but not miR-1-3p expression is modulated by preconditioning in a rat model of myocardial infarction.

Isoflurane (Iso) preconditioning (PC) is known to be cardioprotective against ischemia/reperfusion (I/R) injury. It was previously shown that microRNA-21-5p (miR-21-5p) is regulated by Iso-PC. It is unclear, if expression of cardiac enriched miR-1-3p is also affected by Iso-PC, and associated with activation of HIF1α (hypoxia-inducible factor 1-alpha).  Male Wistar rats (n = 6-8) were randomly assigned to treatment with or without 1 MAC Iso for 30 min, followed by 25 min of regional myocardial ischemia, with 120 min reperfusion. At the end of reperfusion, myocardial expression of miR-1-3p, miR-21-5p and mRNAs of two HIF-1α-dependent genes, VEGF (vascular endothelial growth factor) and HO-1 (heme oxygenase-1), were determined by quantitative PCR. Protein expression of a miR-21 target gene, PDCD4 (programmed cell death protein 4), was assessed by western blot analysis. Infarct sizes were analyzed with triphenyltetrazoliumchloride staining. MiR-21-5p expression was increased by Iso, whereas expression of miR-1-3p was not altered. The expression of VEGF but not HO-1 was induced by Iso. Iso-PC reduced infarct sizes compared to untreated controls. No regulation of miRNA and mRNA expression was detected after I/R. PDCD4 protein expression was not affected after Iso exposure. Expression of miR-21-5p, in contrast to miR-1-3p, is altered during this early time point of Iso-PC. HIF1α signaling seems to be involved in miR-21-5p regulation.

Involvement of MicroRNA-1-FAM83A Axis Dysfunction in the Growth and Motility of Lung Cancer Cells.

Lung cancer is the most prevalent types of cancer and the leading cause of cancer-related deaths worldwide. Among all cancers, lung cancer has the highest incidence, accompanied by a high mortality rate at the advanced stage. Favorable prognostic biomarkers can effectively increase the survival rate in lung cancer. Our results revealed FAM83A (Family with sequence similarity 83, member A) overexpression in lung cancer tissues compared with adjacent normal tissues. Furthermore, high FAM83A expression was closely associated with poor lung cancer survival. Here, through siRNA transfection, we effectively inhibited FAM83A expression in the lung cancer cell lines H1355 and A549. FAM83A knockdown significantly suppressed the proliferation, migration, and invasion ability of these cells. Furthermore, FAM83A knockdown could suppress Epidermal growth factor receptor (EGFR)/Mitogen-activated protein kinase (MAPK)/Choline kinase alpha (CHKA) signaling activation in A549 and H1355. By using a bioinformatics approach, we found that FAM83A overexpression in lung cancer may result from miR-1-3p downregulation. In summary, we identified a novel miR-1-FAM83A axis could partially modulate the EGFR/choline phospholipid metabolism signaling pathway, which suppressed lung cancer growth and motility. Our findings provide new insights for the development of lung cancer therapeutics.

Long noncoding RNA RMRP promotes proliferation and invasion via targeting miR-1-3p in non-small-cell lung cancer.

The long noncoding RNA component of mitochondrial RNA-processing endoribonuclease (lncRNA RMRP) plays an important role in tumor development. In the present study, we determined the regulatory function of RMRP in non-small-cell lung cancer (NSCLC). The NSCLC tissues and the adjacent nontumor tissues were collected for the study. The RMRP expression was detected by quantitative real time-PCR in NSCLC and lung cancer cell lines. The functional validation experiments were performed to determine the role of RMRP on NSCLC progression. In addition, we identified the downstream target miRNAs for RMRP. The results showed that RMRP was elevated in NSCLC tissues and cell lines. High RMRP expression was closely associated with advanced stage for the clinical features and low overall survival in NSCLC patients. Functional assay showed that loss of RMRP markedly inhibited cell proliferation, migration, and invasion. Flow cytometry assay demonstrated that the inhibition of RMRP dramatically induced cell cycle arrest in the G0/G1 phase. Moreover, we found that the role of RMRP on NSCLC cell progression was modulated by the inhibition of miR-1-3p. Collectively, our results demonstrated that the "RMRP-miR-1-3p" axis might promote NSCLC progression. Hence, these investigations will provide a therapeutic target and strategy for the treatment of NSCLC progression.

miR-1-3p and miR-206 sensitizes HGF-induced gefitinib-resistant human lung cancer cells through inhibition of c-Met signalling and EMT.

Hepatocyte growth factor (HGF) overexpression is an important mechanism in acquired epidermal growth factor receptor (EGFR) kinase inhibitor gefitinib resistance in lung cancers with EGFR activating mutations. MiR-1-3p and miR-206 act as suppressors in lung cancer proliferation and metastasis. However, whether miR-1-3p and miR-206 can overcome HGF-induced gefitinib resistance in EGFR mutant lung cancer is not clear. In this study, we showed that miR-1-3p and miR-206 restored the sensitivities of lung cancer cells PC-9 and HCC-827 to gefitinib in present of HGF. For the mechanisms, we demonstrated that both miR-1-3p and miR-206 directly target HGF receptor c-Met in lung cancer. Knockdown of c-Met mimicked the effects of miR-1-3p and miR-206 transfections Meanwhile, c-Met overexpression attenuated the effects of miR-1-3p and miR-206 in HGF-induced gefitinib resistance of lung cancers. Furthermore, we showed that miR-1-3p and miR-206 inhibited c-Met downstream Akt and Erk pathway and blocked HGF-induced epithelial-mesenchymal transition (EMT). Finally, we demonstrated that miR-1-3p and miR-206 can increase gefitinib sensitivity in xenograft mouse models in vivo. Our study for the first time indicated the new function of miR-1-3p and miR-206 in overcoming HGF-induced gefitinib resistance in EGFR mutant lung cancer cell.

MicroRNA-1-3p inhibits the proliferation and migration of oral squamous cell carcinoma cells by targeting DKK1.

We investigated the functional role and mechanism of miR-1-3p and DKK1 in oral squamous cell carcinoma (OSCC) cells. The level of miR-1-3p and DKK1 expression were detected in OSCC tissues and cells using reverse-transcription - quantitative PCR and Western blot. A dual luciferase reporter gene assay was applied to confirm the targeting relationship between miR-1-3p and DKK1. Functional assays, including MTT, Transwell, colony formation, and flow cytometry analysis were conducted to verify their effect on cell progressions. MTT, colony formation, and Transwell assays indicated that the proliferation, migration, and invasion of SCC-4 cells was impaired with high miR-1-3p expression but promoted with high DKK1 expression. The results from cell cycle analysis and annexin-V-PI assays for apoptosis suggested that miR-1-3p suppressed the transit of SCC-4 cells from G0/G1 to S and induced apoptosis. In summary, miR-1-3p suppressed the progression of OSCC by inhibiting DKK1 expression.