MiR-766-3p Suppresses Malignant Behaviors and Stimulates Apoptosis of Colon Cancer Cells via Targeting TGFBI.
Ontology highlight
ABSTRACT: Background
MicroRNAs (miRNAs) can affect the progression of colon cancer cells. A variety of miRNAs, especially miR-766-3p, are proved to be abnormally expressed in colon cancer, but the molecular mechanism of miR-766-3p in this cancer has not yet been fully defined.Methods
Differentially expressed genes in the TCGA-COAD dataset were searched through bioinformatics analysis. MiR-766-3p and TGFBI mRNA levels were measured by qRT-PCR. TGFBI protein expression was measured via Western blot. Targeting relation between miR-766-3p and TGFBI was investigated by dual-luciferase reporter gene assay. Cell proliferation, invasion migration, and apoptosis were detected by cell functional assays.Results
MiR-766-3p was less expressed, while TGFBI was conspicuously highly expressed in colon cancer. MiR-766-3p high expression suppressed cell malignant behaviors and induced cell apoptosis in colon cancer. MiR-766-3p had a targeting relation with TGFBI verified by dual-luciferase assay. The cancer-suppressive impact of miR-766-3p overexpression was attenuated by overexpressing TGFBI.Conclusions
MiR-766-3p/TGFBI axis suppressed malignant behaviors and facilitated apoptosis of colon cancer cells. MiR-766-3p may be an underlying target for colon cancer.
SUBMITTER: Gao J
PROVIDER: S-EPMC8786513 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Background:Medulloblastoma is the most common malignant brain tumor in children. Although the 5-year survival rate is high, patients with relapsed medulloblastoma have a guarded prognosis. HOX transcript antisense RNA (HOTAIR) has been proved to be related to the metastasis of various tumors. Therefore, the molecular mechanism of HOTAIR in medulloblastoma cells was investigated in this study. Methods:HOTAIR was stably silenced in medulloblastoma cells (Daoy and D341). Cell proliferation and apoptosis were detected by 5'-Bromo-2'-deoxyuridine (BrdU) staining, Hoechst 33342 staining, immunohistochemical (IHC), Terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and flow cytometry, respectively. The targeted relationship between HOTAIR/Cyclin-dependent kinase 4 (CDK4) and miR-483-3p were predicted by bioinformatics and confirmed by luciferase reporter assay. Balb/C nude mice were inoculated with shRNA-HOTAIR transfected Daoy cells. Results:We found that the down-regulation of HOTAIR inhibited proliferation and induced apoptosis. Sh-RNA-HOTAIR also inhibited the expression of CKD4. The CDK4 dependent increase of cell proliferation and decrease of cell apoptosis were reversed by shRNA-HOTAIR. Finally, a xenograft model of medulloblastoma in nude mice was built, and the effect of shRNA-HOTAIR on the growth of tumors was analyzed by RT-PCR, immunofluorescence staining, and TUNEL staining. The data suggested interference of HOTAIR inhibited the growth, tumor weight, cell proliferation, and promoted cell apoptosis. Conclusions:Our study altogether demonstrated HOTAIR influence cell proliferation and apoptosis by regulation of miR-483-3p and CDK4 in medulloblastoma cells. HOTAIR can be used as a candidate for potential applications in the treatment of medulloblastoma.
| S-EPMC7396793 | biostudies-literature
Project description:To provide better therapeutic avenues for treating tongue squamous cell carcinoma (TSCC), a series of experiments about the effects of microRNA (miR)-532-3p on TSCC malignant behaviors were carried out. The result showed that miR-532-3p was down-regulated and C-C chemokine receptor 7 (CCR7) was up-regulated in the tumor tissues compared with those in the paired paratumor tissues. Further, expression of miR-532-3p was detected in four TSCC cell lines, TSCCA, TCA8113, CAL-27, and SCC-25. The miR-532-3p mimics and inhibitor were transfected into the CAL-27 and TCA8113 cell lines which were the relatively lowest and highest miR-532-3p expressions, respectively. It was found that the overexpression of miR-532-3p suppressed TSCC cell proliferation, migration, invasion, and promoted apoptosis in vitro, whilst the knockdown of miR-532-3p reversed these behaviors. The bioinformatics predicted that CCR7 was a downstream gene of miR-532-3p, which was confirmed via luciferase assay. Following, the decline of CCR7 in the miR-532-3p mimics group and the rise of CCR7 in the miR-532-3p inhibitor group were also verified. In addition, enhanced cell proliferation, migration and invasion induced by CCR7 were partly restrained by miR-532-3p in TSCC cell. Meanwhile, miR-532-3p attenuated tumourigenesis in vivo due to the reduction of tumor volume and Ki-67 positive rate and the increase of apoptotic cells. Taken together, these findings reveal a pivotal role for the miR-532-3p/CCR7 axis in regulating TSCC, and this novel axis could be suitable for therapeutic intervention in TSCC disease.
| S-EPMC6727182 | biostudies-literature
Project description:Programmed cell death 4 (PDCD4) is a novel tumor suppressor gene and a promising target for anticancer therapies. PDCD4 is frequently downregulated in various human cancers; however, the molecular mechanism accounting for the loss expression of PDCD4 in cancers is not fully understood. In this study, we identified specific targeting sites for miR-208a-3p in the 3'-untranslated region (3'-UTR) of the PDCD4 gene which regulated PDCD4 expression. We demonstrated that miR-208a-3p suppressed apoptosis in gastric cancer cells by targeting PDCD4. We also showed that miR-208a-3p promoted the development of tumor growth in xenograft mice by negatively regulating PDCD4. Taken together, this study revealed a critical role for miR-208a-3p as an oncogenic miRNA in gastric carcinogenesis and it may provide a potential novel target for gastric cancer diagnosis and therapy.
| S-EPMC5341878 | biostudies-literature
Project description:Increasing evidence suggests that long non coding (lnc)RNA and microRNA (miRNA/miR) both regulate the expression of key genes in tumorigenesis and have considerable theranostic potential. Rapid advances in bioinformatics indicate that miRNA may potentially interact with lncRNA to modulate their regulatory roles. miR-148b-3p has been reported to have a vital role in regulating tumor progression. However, the expression pattern of miR-148b-3p in glioma remains largely unknown, and interactions between miR-148b-3p and lncRNA has yet to be identified. The aim of the present study was to insight into the regulatory role of miR-148b-3p in glioma. Using online software, the HOTAIR gene was identified as a possible lncRNA target of miR-148b-3p in the present study. siRNA was used to suppress the expression of HOTAIR and reverse transcription-quantitative polymerase chain reaction was used to detect the expression of miR-148b-3p. The results confirmed that HOTAIR mRNA expression was inversely correlated with miR-148b-3p expression in A172 glioma cells. Furthermore, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the viability of cells, flow cytometry was performed to test cell cycle and a matrigel invasion assay was performed to test cell invasion. The results showed that HOTAIR promotes factors associated with malignancy, including cell proliferation, cell cycle progression and invasion, whereas miR-148b-3p suppresses malignancy. Bioinformatics and luciferase reporter assays showed that miR-148b-3p modulates HOTAIR expression by directly targeting the HOTAIR gene sequence. In summary, the results indicated that miR-148b-3p inhibits malignant biological behaviors of glioma cells by directly targeting HOTAIR. The current data provide important evidence for understanding the key roles of the lncRNA miRNA functional network in glioma.
| S-EPMC4950229 | biostudies-literature
Project description:BACKGROUND:Lung adenocarcinoma (LAD) is a prevalent type of bronchogenic malignant tumor and one of the most critical factors related to human death. Long noncoding RNAs (lncRNAs) are involved in many complex biological processes and have been emerged as extremely important regulators of various cancers. LINC02418, a novel lncRNA, hasn't been mentioned in previous studies on cancer development. Therefore, it's important to define the potential function of LINC02418 in LAD. METHODS:Gene expression was examined by RT-qPCR or western blot. CCK-8, colony formation, TUNEL, and transwell assays were utilized to study the role of LINC02418 in LAD. The interaction of miR-4677-3p with LINC02418 (or KNL1) was verified through luciferase reporter, RIP and RNA pull-down assays. RESULTS:High expression of LINC02418 was observed in LAD specimens and cells. Downregulation of LINC02418 obstructed the proliferation and motility of LAD cells. Moreover, LINC02418 negatively modulated miR-4677-3p expression and miR-4677-3p overexpression could repress cell proliferation and migration. Moreover, kinetochore scaffold 1 (KNL1) expression was negatively modulated by miR-4677-3p but positively regulated by LINC02418. Furthermore, miR-4677-3p could bind with LINC02418 (or KNL1). Finally, KNL1 overexpression reversed the inhibitory function of LINC02418 deficiency in the malignant behaviors of LAD cells. CONCLUSIONS:LINC02418 contributes to the malignancy in LAD via miR-4677-3p/KNL1 signaling, providing a probable therapeutic direction for LAD.
| S-EPMC7427971 | biostudies-literature
Project description:BackgroundMalignant melanoma is an aggressive skin cancer and a tumor of melanocytic origin. Recent studies have suggested that long non-coding RNAs (lncRNAs) play crucial regulatory roles in multiple malignancies, including melanoma. Testis expressed 41 (TEX41) is a relatively new lncRNA whose mechanism in melanoma remains vague.AimsThis study aimed to explore the role and specific mechanism of TEX41 in melanoma.MethodsThe expression of genes involved in this study was determined by qRT-PCR. Functional assays were conducted to analyze the role of relevant genes in melanoma cells. The interaction between TEX41 promoter and IRF4 as well as the relationship among TEX41, miR-103a-3p and C1QB was verified by mechanism assays.ResultsIRF4 up-regulated TEX41 at the transcriptional level in melanoma cells. TEX41 knockdown hindered melanoma cell proliferation, migration and invasion while promoting cell apoptosis. TEX41 bound to miR-103a-3p and regulated C1QB. The suppressive impact of TEX41 depletion on melanoma cell malignant behaviors could be counteracted by miR-103a-3p inhibition or C1QB overexpression. Moreover, IRF4 could facilitate melanoma cell growth via up-regulating C1QB.ConclusionsIRF4-activated TEX41 sequestered miR-103a-3p and modulated C1QB to promote melanoma cell malignant behaviors, for which TEX41 might be regarded as a potential therapeutic target for melanoma.
| S-EPMC8680380 | biostudies-literature
Project description:ObjectiveThe long non-coding RNA zinc finger E-box-binding homeobox 1 antisense 1 (ZEB1-AS1) acts as an oncogenic regulator in many human tumours. In the present study, we identify the role and potential molecular biological mechanisms of ZEB1-AS1 in colon adenocarcinoma (COAD).MethodsQRT-PCR was used to detect the expression of ZEB1-AS1, miR-455-3p and p21-activated kinases 2 (PAK2) in COAD tissues. CCK8 assay, EdU assay, transwell assay and scratch wound assay were used to explore the biological function of ZEB1-AS1 in COAD cells. Bioinformatics, luciferase reporter assays and an RNA pull-down assay were used to demonstrate the mechanism of ZEB1-AS1. We further explore the role of ZEB1-AS1 in vivo though xenograft tumour assay.ResultsWe found that ZEB1-AS1 expression was significantly up-regulated in COAD tissues, and high ZEB1-AS1 level was correlated with the poor prognosis of COAD patients. MiR-455-3p plays an anti-cancer role in COAD by targeting PAK2. We confirmed that ZEB1-AS1 promotes PAK2 expression by sponging miR-455-3p, thus facilitating COAD cell growth and metastasis.ConclusionsTo sum up, this result illustrates the novel molecular mechanism of ZEB1-AS1 in COAD and provides a new target for the diagnosis and treatment of COAD patients.
| S-EPMC6985675 | biostudies-literature
Project description:BackgroundThe competing endogenous RNA (ceRNA) networks of long non-coding RNAs (lncRNAs) and microRNAs (miRs) have aroused wide concerns. The study aims to investigate the roles of lncRNA DANCR-associated ceRNA network in the growth and behaviors of colon cancer (CC) cells.MethodsDifferentially expressed lncRNAs between CC and paracancerous tissues were analyzed using microarrays and RT-qPCR. Follow-up studies were conducted to evaluate the correlation between DANCR expression and prognosis of CC patients. Loss-of-functions of DANCR were performed to identify its role in the malignant behaviors of CC cells. Sub-cellular localization of DANCR and the potential targets of DANCR were predicted and validated. Cells with inhibited DANCR were implanted into nude mice to evaluate the tumor formation and metastasis in vivo.ResultsDANCR was highly-expressed in CC tissues and cell lines, and higher levels of DANCR were linked with worse prognosis and less survival time of CC patients. Silencing of DANCR inhibited proliferation, viability, metastasis and resistance to death of CC cells. DANCR was found to be sub-localized in cytoplasmic matrix and to mediate murine double minute 2 (MDM2) expression through sponging miR-518a-3p in CC cells, during which the Smad2/3 signaling was activated. Likewise, silencing of DANCR in CC cells inhibited tumor formation and metastasis in vivo.ConclusionThis study provided evidence that silencing of DANCR might inhibit the growth and metastasis of CC cells through the DANCR/miR-518a-3p/MDM2 ceRNA network and the defect of Smad2/3 while activation of the p53 signaling pathways. This study may offer novel insights in CC treatment.
| S-EPMC7236548 | biostudies-literature
Project description:Purpose:Long non-coding RNAs have been found to be involved in bladder cancer development. This article studied LINC00963 effects on bladder cancer progression to provide a novel treatment target. Patients and Methods:Totally 56 bladder cancer patients participated in this research. Bladder cancer cells were transfected. Cell counting kit 8 assay and clone formation experiment were used for cell viability and colony formation detection. Cell migration and invasion were determined by Transwell experiment. LINC00963 distribution was explored by cytoplasmic and nuclear extract isolation and quantitative real-time polymerase chain reaction. Luciferase reporter experiment and RNA pulldown experiment were performed to detect the relationship between these two genes. The cancer genome atlas analysis was used for the detection of metastasis-associated protein 1 (MTA1) expression in bladder cancer. Results:LINC00963 was seriously up-regulated in bladder cancer patients. High LINC00963 expression indicated high histological grade and low survival. LINC00963 was obviously up-regulated in bladder cancer cells. Knockdown of LINC00963 significantly reduced bladder cancer cells viability, colony formation, migration and invasion. Luciferase reporter experiment and RNA pulldown experiment revealed that LINC00963 promoted MTA1 expression via directly inhibiting miR-766-3p. MTA1 was up-regulated in bladder cancer patients. MTA1 up-regulation reversed the inhibitory effect of LINC00963 knockdown on bladder cancer cell viability, migration and invasion. Conclusion:LINC00963 functions as an oncogene in bladder cancer by regulating the miR-766-3p/MTA1 axis.
| S-EPMC7229805 | biostudies-literature
Project description:BackgroundLong noncoding RNA (lncRNA) TUG1 has been reported to display a pivotal role in the tumorigenesis and malignant progression of various types of cancers, including stomach adenocarcinoma (STAD). However, the contribution of aberrant expression of TUG1 and the mechanism by which it serves as a competing endogenous RNA (ceRNA) in STAD remains largely obscure.MethodsThe human STAD cell lines (MGC-803 and AGS), human normal gastric epithelial cell line (GES-1), human umbilical vein endothelial cells (HUVECs), and human embryonic kidney cells (HEK293T) were purchased and cultured to investigate the roles of TUG1 in STAD. Twenty BALB/c nude mice were purchased to establish a xenograft model to explore the roles of TUG1 in vivo.ResultsBioinformatics analysis revealed that TUG1 was upregulated in STAD, of which expression was negatively and positively correlated with miR-29c-3p and VEGFA, respectively. Functional analyses indicated that TUG1 functioned as an oncogene to promote malignant behaviors (proliferation, migration, and angiogenesis) of STAD cells; whereas miR-29c-3p exerted the opposite role. Mechanistically, the interaction between miR-29c-3p with TUG1 and VEGFA was demonstrated. It was observed that miR-29c-3p could reverse the TUG1-induced promotion effect on cell proliferation, migration, and angiogenesis in STAD. Furthermore, TUG1 overexpression promoted STAD cell proliferation, metastasis, and angiogenesis, whereas VEGFA silence restored these effects, both in vitro and in vivo.ConclusionThis finding confirmed that lncRNA TUG1 acts as a ceRNA for miR-29c-3p to promote tumor progression and angiogenesis by upregulating VEGFA, indicating TUG1 as a therapeutic target in STAD management.
| S-EPMC8649340 | biostudies-literature