Project description:Long noncoding RNAs have been widely accepted to play important roles in acute myocardial infarction (AMI). The dysregulation of cyclin-dependent kinase inhibitor 2B antisense RNA 1 (ANRIL) was discovered in AMI patients. Nevertheless, the detailed role and molecular mechanisms of ANRIL in AMI remain indistinct. The levels of ANRIL, miR-195-5p and Bcl-2 mRNA were determined by qRT-PCR. western blot was performed to assess the expression of Bcl-2, Bax, Cyclin D1 and p21. Cell proliferation was detected by CCK-8 assay, and cell apoptosis was measured by flow cytometry. The targeted correlation between ANRIL and miR-195-5p was confirmed by the dual-luciferase reporter and RNA pull-down assays. Our data revealed that ANRIL was downregulated and miR-195-5p was upregulated in the serum of AMI patients and hypoxia/reoxygenation (H/R)-induced myocardial cells. ANRIL upregulation or miR-195-5p knockdown alleviated H/R-induced myocardial cell injury. Moreover, ANRIL sequestered miR-195-5p by acting as a sponge of miR-195-5p. ANRIL upregulated Bcl-2 expression by sponging miR-195-5p. Additionally, ANRIL overexpression alleviated H/R-induced myocardial cell injury by upregulating Bcl-2. In conclusion, our study indicated that ANRIL upregulation alleviated H/R-induced myocardial cell injury partially through sponging miR-195-5p and upregulating Bcl-2, highlighting its role as a promising mediator for new therapies for AMI treatment.
Project description:TMPRSS11D is a member of the type II transmembrane serine proteases (TTSPs) family that is implicated in the development and progression of several cancers. However, the biological roles of TMPRSS11D in cervical cancer have not been investigated. In the present study, we detected the expression levels of TMPRSS11D in human cervical cancer tissues and cell lines. The results showed that TMPRSS11D expression was significantly upregulated in cervical cancer tissues as compared to the adjacent normal tissues. Besides, TMPRSS11D was highly expressed in human cervical cancer cell lines. Then we knocked down TMPRSS11D in cervical cancer cell lines to evaluate the effects of TMPRSS11D knockdown on cervical cancer cells. The results showed that knockdown of TMPRSS11D significantly suppressed cell proliferation, migration and invasion in cervical cancer cell lines. Furthermore, the data revealed that TMPRSS11D knockdown prevented epithelial-mesenchymal transition (EMT), as proved by the increased E-cadherin expression, as well as decreased N-cadherin and fibronectin expressions. Additionally, knockdown of TMPRSS11D inhibited the activation of the PI3K/Akt pathway in cervical cancer cells. Furthermore, insulin-like growth factor-1 (IGF-1) treatment reversed the inhibitory effects of TMPRSS11D knockdown on cell proliferation and migration. Collectively, knockdown of TMPRSS11D exerted anti-tumor activity, at least in part, via inhibiting the PI3K/Akt pathway. These findings indicated that TMPRSS11D might serve as a novel therapeutic target for the treatment of cervical cancer.
Project description:Long noncoding RNAs (lncRNAs) are implicated in the development of chemoresistance in many cancers. However, the effect and mechanism of lncRNA antisense noncoding RNA in the INK4 locus (ANRIL) on cisplatin (CDDP) resistance in non-small cell lung cancer (NSCLC) remain unclear. The levels of ANRIL, microRNA (miR)-656-3p and sex-determining region Y-related high-mobility group box 4 (SOX4) in NSCLC tissues and cells were detected by quantitative real-time polymerase chain reaction or western blotting. Cell viability, apoptosis, migration and epithelial-to-mesenchymal transition (EMT) were assessed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT assay), flow cytometry, trans-well assays and western blotting, respectively. The xenograft model was established using CDDP-resistant NSCLC cells. The target association between miR-656-3p and ANRIL or SOX4 was validated by luciferase reporter assay and RNA immunoprecipitation. ANRIL expression was increased in CDDP-resistant NSCLC tissues and cells. Knockdown of ANRIL decreased cell viability, migration and EMT but induced apoptosis in CDDP-resistant NSCLC cells. Moreover, silencing of ANRIL reduced xenograft tumor growth in vivo. miR-656-3p was targeted by ANRIL and its exhaustion attenuated the suppressive role of ANRIL knockdown in CDDP resistance in NSCLC cells. SOX4 acted as a target of miR-656-3p and was positively regulated by ANRIL. Collectively, interference of ANRIL repressed CDDP resistance through promoting apoptosis and inhibiting cell viability, migration and EMT by up-regulating miR-656-3p and down-regulating SOX4, indicating a new target to improve the chemotherapeutic efficacy in NSCLC.
Project description:Statement of RetractionWe, the Editors and Publisher of the journal Cell Cycle, have retracted the following article:Rui Li, Xia Qiu, Mei He, Jing Qiao, Jing He, and Mei Zhong. METTL3-mediated mature miR-497-5p/195-5p inhibits trophoblast migration and invasion by targeting WWP1 in preeclampsia. Cell Cycle. 2021. doi: 10.1080/15384101.2021.1982527.Since publication, the authors have raised significant concerns about the reliability of the data presented in the article. As the Editor and Publisher also have concerns about the integrity of the reported results, all parties have agreed to retract the article to ensure correction of the scholarly record.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as 'Retracted'.
Project description:MiR-671-5p is encoded by a gene localized at 7q36.1, a region amplified in human glioblastoma multiforme (GBM), the most malignant brain cancer. To investigate whether expression of miR-671-5p were altered in GBM, we analyzed biopsies from a cohort of forty-five GBM patients and from five GBM cell lines. Our data show significant overexpression of miR-671-5p in both biopsies and cell lines. By exploiting specific miRNA mimics and inhibitors, we demonstrated that miR-671-5p overexpression significantly increases migration and to a less extent proliferation rates of GBM cells. Through a combined in silico and in vitro approach, we identified CDR1-AS, CDR1, VSNL1 as downstream miR-671-5p targets in GBM. Expression of these genes significantly decreased both in GBM biopsies and cell lines and negatively correlated with that of miR-671-5p. Based on our data, we propose that the axis miR-671-5p / CDR1-AS / CDR1 / VSNL1 is functionally altered in GBM cells and is involved in the modification of their biopathological profile.
Project description:Prostate cancer (PCa) is the second cause of death due to malignancy among men, and metastasis is the leading cause of mortality in patients with PCa. MicroRNAs (miRNAs) play important regulatory roles in tumor development and metastasis. Here, we identified 13 miRNAs related to PCa metastasis by bioinformatics analysis. Moreover, we found that miR-671-5p was increased in metastatic PCa tissues, and its high expression indicated poor prognosis of PCa. MiR-671-5p could facilitate PCa cells proliferation, migration, and invasion in vitro and vivo. We confirmed that miR-671-5p directly bound to the 3' untranslated regions of NFIA mRNA, and NFIA directly bound to the CRYAB promoter. High expression of NFIA and CRYAB negatively correlated with the advanced clinicopathological characteristics and metastasis status of PCa patients. Our study demonstrated that miR-671-5p promoted PCa development and metastasis by suppressing NFIA/ CRYAB axis.
Project description:In the initiation and evolution of human cancers, circular RNAs (circRNAs) act as crucial regulators. The aim of this report was to ascertain the functional mechanisms of circRNA plasmacytoma variant translocation 1 (circPVT1) in the metastasis and chemoresistance of non-small cell lung cancer (NSCLC). The levels of circPVT1, microRNA-181a-5p (miR-181a-5p) and non-inherited maternal antigens-related kinase 7 (NEK7) were examined via quantitative real-time polymerase chain reaction (qRT-PCR). The levels of the associated proteins were determined through western blot. Cell counting kit-8 (CCK-8) and flow cytometry were used to assess the half inhibitory concentration (IC50) of cisplatin and cell apoptosis, respectively. Cell invasion was detected by transwell assay. A dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were used to confirm the target relation. The impact of circPVT1 on cisplatin chemoresistance in vivo was investigated using xenograft experiments. CircPVT1 and NEK7 were up-regulated and miR-181a-5p was down-regulated in NSCLC. CircPVT1 knockdown refrained the cisplatin chemoresistance and metastasis of NSCLC cells. MiR-181a-5p was a target of circPVT1 and circPVT1 inhibition alleviated the effects of a miR-181a-5p inhibitor on NSCLC cells. The decrease of circPVT1 accentuated the si-NEK7-inhibited metastasis by the miR-181a-5p/NEK7 axis and relieved the 3-methyladenine (3-MA)-promoted cisplatin chemoresistance by miR-181a-5p-mediated autophagy. Down-regulation of circPVT1 facilitated the cisplatin sensitivity of NSCLC cells in vivo. Due to the modulation of cell metastasis via the miR-181a-5p/NEK7 axis and cisplatin chemoresistance by miR-181a-5p-mediated autophagy in NSCLC, circPVT1 might act as an appreciable therapeutic marker for NSCLC.
Project description:Glioma is an aggressive brain cancer with poor prognosis and high invasiveness. Dysregulation of circular RNAs (circRNAs) has been widely discovered in various cancers, including glioma. However, the molecular mechanism of circ_0034642 in glioma is still unclear. The expression of circ_0034642, microRNA (miR)-625-5p and transgelin-2 (TAGLN2) in glioma tumors and cells was detected by performing a quantitative real-time polymerase chain reaction (qRT-PCR). The stability of circ_0034642 was determined by carrying out RNase R treatment. Cell proliferation was evaluated by performing the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Glycolysis was analyzed by measuring the extracellular acidification rate (ECAR) using glucose detection and lactic acid detection kits. Cell migration and invasion were determined by performing the transwell assay. Protein expression levels of the proteins hexokinase 2 (HK2), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9) and TAGLN2 were analyzed using western blots. The interaction between miR-625-5p and circ_0034642 or TAGLN2 was proved using a dual-luciferase reporter system. Animal models were established by subcutaneously injecting glioma cells stably transfected with sh-NC or sh-circ_0034642. Circ_0034642 and TAGLN2 were overexpressed whereas miR-625-5p was expressed at low levels in glioma tumors and cells. Moreover, circ_0034642 and TAGLN2 were upregulated while miR-625-5p was downregulated under hypoxic conditions in a time-dependent manner. Next, elimination of circ_0034642 was shown to inhibit cell glycolysis, proliferation, migration and invasion under hypoxic conditions in gliomas. Then, we found that circ_0034642 acted as a "sponge" of miR-625-5p while TAGLN2 acted as a target of miR-625-5p. In addition, recovery of circ_0034642 attenuated the repression mediated by miR-625-5p on glioma cell glycolysis and progression under hypoxic conditions. Meanwhile, an inhibitor of miR-625-5p alleviated TAGLN2 deficiency-induced inhibition of glioma cell development under hypoxic conditions. We also discovered that circ_0034642 could interact with miR-625-5p and further alter the expression of TAGLN2. Lastly, a circ_0034642 knockdown hindered tumor growth in vivo by regulating the miR-625-5p/TAGLN2 axis. Enhanced expression of circ_0034642 was found to promote cell glycolysis, proliferation, migration and invasion under hypoxic conditions in gliomas by sponging miR-625-5p to improve TAGLN2 expression, providing prospective biomarkers for the diagnosis of glioma.
Project description:Background: Dysregulated lncRNA expression contributes to the pathogenesis of human tumors via the lncRNAs functioning as oncogenes or tumor suppressors. Small nucleolar RNA host gene 3 (SNHG3) was demonstrated to be upregulated in breast cancer cells. However, the detailed roles and molecular mechanism of SNHG3 in breast cancer are largely unknown. Methods: The expression of SNHG3, miR-101, and zinc finger E-box-binding protein 1 (ZEB1) in breast cancer tissues and cells was detected using qRT-PCR. The effects of SNHG3 on cell proliferation and invasion were evaluated using MTT, EdU, and cell invasion assays. The protein levels of Ki-67, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase MMP-2, and MMP-9 were analyzed using western blot analysis. A luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to explore the interaction between SNHG3, ZEB1 and miR-101. A subcellular fractionation assay was used to detect the subcellular location of SNHG3. Xenograft tumor experiments were conducted to verify the role and mechanism of SNHG3 in breast cancer in vivo. Results: SNHG3 expression was upregulated in breast cancer tissues and correlated with poor prognosis. SNHG3 knockdown suppressed breast cancer cell proliferation and invasion, which was further demonstrated by high levels of proliferation marker proteins Ki-67/PCNA and metastasis-related proteins MMP-2/MMP-9. Additionally, SNHG3 was located in the cytoplasm of breast cancer cells. SNHG3 functioned as a molecular sponge for miR-101 in breast cancer cells. miR-101 was downregulated in breast cancer tissues and negatively correlated with SNHG3 expression. Moreover, ZEB1, a target of miR-101, was positively regulated by SNHG3 in breast cancer cells. ZEB1 mRNA expression was upregulated in breast cancer tissues and positively correlated with SNHG3 expression. Mechanistically, SNHG3 knockdown suppressed cell proliferation and invasion by upregulation of miR-101 and downregulation of ZEB1 expression in breast cancer cells in vitro and in vivo. Conclusion: SNHG3 promoted proliferation and invasion by regulating the miR-101/ZEB1 axis in breast cancer.