Retracted Article: Long non-coding RNA MEG3 inhibits cell proliferation,migration, invasion and enhances apoptosis in non-small cell lung cancer cells by regulating the miR-31-5p/TIMP3 axis

Non-small cell lung cancer (NSCLC) is a malignant lung cancer and accounts for 80% of lung cancer-related deaths. Long non-coding RNA maternally expressed gene 3 (MEG3) has been identified as a tumor suppressor in multiple cancers. However, the regulatory mechanism of MEG3 in NSCLC development is still largely unknown. The expression levels of MEG3, microRNA-31-5p (miR-31-5p) and tissue inhibitor of metalloproteinase 3 (TIMP3) in NSCLC tumors and cells were measured by quantitative real time polymerase chain reaction (qRT-PCR). Cell viability, apoptosis, migration and invasion were detected by cell counting kit-8 (CCK-8), flow cytometry, western blotting and transwell assays, respectively. Xenograft mouse models were established by subcutaneously injecting NSCLC cells stably transfected with Lenti-pcDNA or Lenti-MEG3. The interaction between miR-31-5p and MEG3 or TIMP3 was validated by luciferase reporter and RNA immunoprecipitation (RIP) assays. MEG3 and TIMP3 levels were up-regulated, whereas miR-31-5p expression was down-regulated in NSCLC tumors and cells compared with normal tissues and cells. Overexpression of MEG3 repressed cell proliferation, migration and invasion, but induced apoptosis in NSCLC cells. More importantly, MEG3 effectively hindered tumor growth in vivo. Next, luciferase reporter and RIP assays confirmed the interaction between miR-31-5p and MEG3 or TIMP3. Pearson''s correlation coefficient revealed that miR-31-5p was inversely correlated with MEG3 or TIMP3. Rescue experiments indicated that MEG3 regulated TIMP3 expression by sponging miR-31-5p in NSCLC cells. Thus, MEG3 inhibited cell proliferation, migration and invasion, but enhanced apoptosis in NSCLC cells through up-regulating TIMP3 expression by regulating miR-31-5p, indicating novel biomarkers for the therapy of NSCLC.

Non-small cell lung cancer (NSCLC) is a malignant lung cancer and accounts for 80% of lung cancer-related deaths.     

Retracted Article: SNHG3 promotes proliferation and invasion by regulating the miR-101/ZEB1 axis in breast cancer

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.

In the present study, we investigated the expression and functional roles of SNHG3 in breast cancer cells, as well as the underlying mechanism of SNHG3 involved in the progression of breast cancer in vitro and in vivo.     

Correction: Long non-coding RNA MEG3 inhibits cell proliferation,migration, invasion and enhances apoptosis in non-small cell lung cancer cells by regulating the miR-31-5p/TIMP3 axis

Correction for ‘Long non-coding RNA MEG3 inhibits cell proliferation, migration, invasion and enhances apoptosis in non-small cell lung cancer cells by regulating the miR-31-5p/TIMP3 axis’ by Kui Li et al., RSC Adv., 2019, 9, 38200–38208, DOI: 10.1039/C9RA07880K.

In the published paper the Acknowledgements section was omitted; this should read:This work was supported by Major Scientific and Technological Projects of Guangzhou Science and Technology Plan Projects (No. 201802020004).The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Retracted Article: Long non-coding RNA KCNQ1OT1 regulates cell proliferation,apoptosis and chemo-sensitivity through modulating the miR-186-5p/NCAM1 axis in acute myeloid leukemia cells

Recent studies show that lncRNA KCNQ1OT1 and microRNA-186-5p (miR-186-5p) are involved in various human cancers. Moreover, it is reported that KCNQ1OT1 expression is upregulated in acute myeloid leukemia (AML). However, their roles in AML remain unknown. This study aimed to reveal the functional mechanism of KCNQ1OT1 and miR-186-5p in AML development. Quantitative real time polymerase chain reaction (qRT-PCR) was performed to detect the levels of genes. Cell proliferation and apoptosis were assessed by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry analysis respectively. A western blot assay was carried out to examine the protein levels. In addition, the interaction between miR-186-5p and KCNQ1OT1 or neural cell adhesion molecule 1 (NCAM1) was predicted by bioinformatics analysis tool starbase2.0 and confirmed by the dual luciferase reporter assay. KCNQ1OT1 and NCAM1 expressions were increased and miR-186-5p expression was decreased in AML samples and cells. The depletion of KCNQ1OT1 inhibited cell proliferation, and promoted apoptosis and chemo-sensitivity in AML. In addition, the upregulation of miR-186-5p suppressed AML cell proliferation, and induced apoptosis and chemo-sensitivity. Interestingly, KCNQ1OT1 directly downregulated miR-186-5p expression and miR-186-5p decreased NCAM1 expression by binding to the 3′ untranslated region (UTR) of NCAM1 mRNA. Furthermore, miR-186-5p knockdown or NCAM1 overexpression reversed the effects of KCNQ1OT1 depletion on AML cell progression. Our results firstly revealed a linear relationship between KCNQ1OT1, miR-186-5p, and NCAM1, and demonstrated that KCNQ1OT1 mediated AML cell progression via regulating the miR-186-5p/NCAM1 axis, revealing functional mechanisms of KCNQ1OT1 and miR-186-5p in AML development.

Recent studies show that lncRNA KCNQ1OT1 and microRNA-186-5p (miR-186-5p) are involved in various human cancers.     

Retracted Article: Long noncoding RNA PCA3 regulates glycolysis,viability and apoptosis by mediating the miR-1/CDK4 axis in prostate cancer

Prostate cancer is one of the common tumor malignancies in men worldwide. Although long noncoding RNAs (lncRNAs) have been demonstrated to play essential roles in the progression of prostate cancer, the roles and potential mechanism of lncRNA prostate cancer antigen 3 (PCA3) remain poorly understood. In the present study, we investigated the role of PCA3 in aerobic glycolysis, viability and apoptosis in prostate cancer cells and probed the interaction between PCA3 and microRNA-1 (miR-1)/cyclin-dependent kinase 4 (CDK4). Here we found that PCA3 and CDK4 were up-regulated while miR-1 was down-regulated in prostate cancer tissues and cells. Moreover, knockdown of PCA3 inhibited aerobic glycolysis and viability and induced apoptosis in prostate cancer cells. Intriguingly, PCA3 was bound to miR-1 and inhibition of miR-1 reversed the regulatory effect of PCA3 knockdown on aerobic glycolysis, viability and apoptosis in prostate cancer cells. Besides, CDK4 was indicated as a target of miR-1 and it was regulated by PCA3 through functioning as a competing endogenous RNA (ceRNA) of miR-1 in prostate cancer cells. The results indicated that PCA3 might drive aerobic glycolysis, viability and apoptosis by regulating the miR-1/CDK4 axis in prostate cancer cells, providing a promising avenue for treatment of prostate cancer.

We proved that PCA3 regulated aerobic glycolysis, viability and apoptosis by regulating the miR-1/CDK4 axis in prostate cancer cells.     

Retracted Article: Long noncoding RNA DLEU1 promotes cell proliferation and migration of Wilms tumor through the miR-300/HOXC8 axis

Wilms tumor (nephroblastoma) is the most common primary renal tumor occurring in children. Long noncoding RNA (lncRNA) deleted in lymphocytic leukemia 1 (DLEU1) is an identified cancer-associated lncRNA that plays an important role in various cancers. However, the role of DLEU1 in Wilms tumor remains unclear. In the present study, we examined the expression and role of DLEU1 in Wilms tumor. We demonstrated that DLEU1 expression was upregulated in Wilms tumor tissues and cell lines. Knockdown of DLEU1 significantly inhibited the proliferation, migration and invasion of GHINK-1 cells. Furthermore, DLEU1 directly sponged miR-300 and regulated the expression level of miR-300 in GHINK-1 cells. Inhibition of miR-300 reversed the inhibitory effects of DLEU1 downregulation on cell proliferation, migration and invasion. Homeobox C8 (HOXC8) was found to be a target gene of miR-300 and mediated the role of miR-300 in GHINK-1 cells. In conclusion, these findings indicated that DLEU1 executed an oncogenic role in Wilms tumor via regulating the miR-300/HOXC8 axis, indicating that DLEU1 might be a therapeutic target for the treatment of Wilms tumor.

Wilms tumor (nephroblastoma) is the most common primary renal tumor occurring in children.     

Retracted Article: Long non-coding RNA KCNQ1OT1 promotes osteosarcoma progression by increasing β-catenin activity

Objective: Long non-coding RNA KCNQ1OT1 has been associated with the development of different types of cancers. The present research investigated the role of KCNQ1OT1 in osteosarcoma. Methods: Expression level of KCNQ1OT1 in osteosarcoma and paired non-cancerous tissue specimens from 56 osteosarcoma patients and its association with patients'' clinicopathological features was investigated. KCNQ1OT1 overexpression and knockdown in primary-cultured osteosarcoma cells was constructed by lentiviral transduction. Influence of KCNQ1OT1 overexpression or knockdown on osteosarcoma cell growth, apoptosis, migration, invasion, epithelial-to-mesenchymal transition and beta-catenin activation was investigated. Results: Expression of KCNQ1OT1 in osteosarcoma tissue specimens was significantly increased in comparison to that in adjacent counterparts. High expression of KCNQ1OT1 significantly associated with osteosarcoma progression and patients'' decreased survival. Overexpression of KCNQ1OT1 significantly increased osteosarcoma cell growth, proliferation, migration, invasion, epithelial-to-mesenchymal transition and beta-catenin activation while reducing cell apoptosis in vitro, and KCNQ1OT1 knockdown showed opposite effects. Inhibition of beta-catenin/TCF activity by ICG-001 treatment significantly attenuated the promoting effect of KCNQ1OT1 overexpression on osteosarcoma cell malignancy described above. Conclusion: KCNQ1OT1 might be a potential prognostic factor in osteosarcoma. High expression of KCNQ1OT1 might promote osteosarcoma development by increasing the activation of WNT/beta-catenin signaling pathway.

Long non-coding RNA KCNQ1OT1 has been associated with the development of different types of cancers.     

Retracted Article: Daphnetin inhibits proliferation and glycolysis in colorectal cancer cells by regulating the PI3K/Akt signaling pathway

Daphnetin (7,8-dihydroxycoumarin), a natural coumarin compound, has shown antitumor and energy metabolism regulatory activities. However, the effects of daphnetin on cell proliferation, migration, and glucose metabolism in colorectal cancer (CRC) cells remains unknown. In this study, the effects of daphnetin on CRC cell proliferation, migration, and glucose metabolism have been examined. The results showed that daphnetin inhibited the proliferation, migration, and invasion of CRC cells, and induced CRC cell apoptosis. Furthermore, daphnetin suppressed intracellular glucose and lactate production, and downregulated the expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) in CRC cells. Furthermore, daphnetin prevented activation of the PI3K/Akt pathway in CRC cells. These findings demonstrated that daphnetin inhibited the proliferation, migration and glucose metabolism in CRC cells by suppressing the PI3K/Akt signaling pathway. Therefore, daphnetin has potential as a novel anticancer agent for CRC treatment.

Daphnetin (7,8-dihydroxycoumarin), a natural coumarin compound, has shown antitumor and energy metabolism regulatory activities.     

Long non-coding RNA PVT1 facilitates cell proliferation by epigenetically regulating FOXF1 in breast cancer

Background: plasmacytoma variant translocation 1 (PVT1) has been identified as an oncogenic long non-coding RNA (lncRNA) in multiple cancers including breast cancer. However, its molecular basis has not been exhaustively elucidated. Methods: RT-qPCR assay was used to detect PVT1 expression in tissues and cells. The effect of PVT1 and FOXF1 on breast cancer cell proliferation was assessed by MTT, colony formation and cell cycle assays. Cell apoptotic rate was measured by flow cytometry via double-staining of Annexin V-FITC and PI. The protein expression patterns of forkhead box f1 (FOXF1) and enhancer of zeste homolog 2 (EZH2) were detected using western blot assays. The subcellular location of PVT1 was analyzed using subcellular fractionation assays. The interaction between PVT1 and EZH2 were demonstrated by RNA-protein pull down and RIP assays. ChIP assay was used to explore whether PVT1 affected FOXF1 expression by recruiting EZH2. In vivo assays were performed to further investigate the roles of PVT1 in breast cancer tumorigenesis. Results: PVT1 expression was elevated in breast cancer tissues and cells. Moreover, higher PVT1 level was positively associated with aggressive pathological status and poor prognosis of breast cancer. PVT1 knockdown suppressed proliferation and induced apoptosis in breast cancer cells. PVT1 silenced FOXF1 expression by recruiting EZH2 to the promoter region of FOXF1, resulting in the increase of H3K27me3 level. EZH2 inhibitor EPZ005687 counteracted PVT1-mediated enrichment effect on H3K27me3 and EZH2 to FOXF1 promoter region. FOXF1 overexpression hampered proliferation and facilitated apoptosis in breast cancer cells. Furthermore, down-regulation of FOXF1 partly abrogated PVT1-knockdown-mediated anti-proliferation and pro-apoptosis effect in breast cancer cells. Finally, PVT1 deficiency suppressed tumor growth by promoting FOXF1 expression in vivo. Conclusion: PVT1 promoted cell proliferation and suppressed apoptosis by epigenetically silencing FOXF1 expression through EZH2 in breast cancer.

Plasmacytoma variant translocation 1 (PVT1) expression was elevated in breast cancer tissues and correlated to breast cancer progression and prognosis.     

Retracted Article: Long noncoding RNA ANRIL knockdown increases sensitivity of non-small cell lung cancer to cisplatin by regulating the miR-656-3p/SOX4 axis

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.

Long noncoding RNAs (lncRNAs) are implicated in the development of chemoresistance in many cancers.     

Retracted Article: Overexpression of PCDH8 inhibits proliferation and invasion,and induces apoptosis in papillary thyroid cancer cells

Protocadherin8 (PCDH8), a member of the protocadherin (PCDH) family, is involved in the progression of several types of cancers. However, the expression and biological roles of PCDH8 in papillary thyroid carcinoma (PTC) remain largely unknown. Therefore, in the present study, we detected the expression of PCDH8 in human PTC tissues and cell lines, and evaluated its role in PTC cells. Our results demonstrated that PCDH8 was lowly expressed in human PTC tissues and cell lines. In addition, ectopic expression of PCDH8 efficiently inhibited the proliferation, migration and invasion of PTC cells, as well as prevented the epithelial-mesenchymal transition (EMT) phenotype in PTC cells. Furthermore, PCDH8 efficiently induced apoptosis and autophagy in PTC cells. Mechanistically, overexpression of PCDH8 significantly prevented the activation of the Wnt/β-catenin pathway in PTC cells. Taken together, these findings showed that overexpression of PCDH8 inhibits proliferation and migration/invasion, and induces apoptosis of PTC cells through the Wnt/β-catenin signaling pathway.

Protocadherin8 (PCDH8), a member of the protocadherin (PCDH) family, is involved in the progression of several types of cancers.     

长链非编码RNA CRNDE 通过调控NPHS1的表达促进糖尿病肾病足细胞损伤

目的 探讨长链非编码 RNA（lncRNA）在糖尿病肾病（DN）发生发展中的作用。方法 收集临床肾活组织检查标本,采用RNA-seq 测序技术检测DN组与正常对照组（NC组）肾组织中差异表达的lncRNA及mRNA。通过 GO、KEGG数据库分析差异表达mRNA的生物学功能,并通过共表达网络分析预测差异表达lncRNA的相互作用基因。采用实时荧光定量 PCR（qRT-PCR）检测目标lncRNA、mRNA 在DN肾组织中的相对表达水平。结果 RNA-seq 测序结果表明,与NC组相比,DN组共有353个差异表达的lncRNA,其中224个表达上调,129个表达下调。qRT-PCR 结果显示,DN组中CRNDE、PVT1和 BLZF2P 相对表达水平较NC组升高（P均< 0.001）,而WT1-AS、TARID 和 ST13P6相对表达水平较NC组降低（P均< 0.001）。共表达网络分析及双变量相关分析显示lncRNA CRNDE 与 NPHS1（编码的 nephrin 是足细胞结构完整性和发挥功能的决定性关键蛋白）呈负相关。结论 lncRNA CRNDE 在DN肾组织中表达明显升高,且与 NPHS1存在负相关关系,lncRNA CRNDE 可能通过调控 NPHS1 的表达促进DN足细胞损伤。     

Retracted Article: PVT1 depletion protects cartilage ATDC5 cells against LPS-induced inflammatory injury by regulating the miR-24/ADAMTS5 axis

Background: Osteoarthritis is a common chronic arthritis among adults and cartilage dysfunction is largely responsible for osteoarthritis development. Long noncoding RNAs (lncRNAs) have been reported to be related to osteoarthritis progression. However, the mechanism that underlies the effect of lncRNA plasmacytoma variant translocation 1 (PVT1) on inflammatory injury in cartilage ATDC5 cells remains elusive. Methods: The quantity of PVT1 and microRNA-24 (miR-24) was detected in human cartilage ATDC5 cells after transfection of si-PVT1, si-con, PVT1 or pcDNA and lipopolysaccharide (LPS) treatment for 12 h. Inflammatory injury was investigated using cell viability, apoptosis and secretion of inflammatory cytokines. The interaction of miR-24 with PVT1 or a disintegrin-like metalloproteinase with thrombospondin motifs 5 (ADAMTS5) was probed by bioinformatics, luciferase activity, RNA pull down and Ago1 RNA immunoprecipitation (RIP) assays. The effect of PVT1 and miR-24 on ADAMTS5 expression was evaluated in ATDC5 cells by western blotting (WB). Results: Treatment of LPS induced elevated PVT1 and reduced miR-24 expression in ATDC5 cells. Moreover, LPS inhibited cell viability, increased apoptosis and inflammatory cytokine production. However, PVT1 depletion attenuated LPS-induced inflammatory injury in ATDC5 cells. In addition, miR-24 directly bound to PVT1 and its deficiency reversed the effect of PVT1 deletion in LPS-treated ATDC5 cells. Furthermore, ADAMTS5 was a target of miR-24 and aberrant expression of ADAMTS5 was regulated by PVT1 and miR-24. Conclusion: PVT1 abrogation protected against LPS-induced inflammatory injury in ATDC5 cells by coordinating with the miR-24/ADAMTS5 axis, opening up a novel avenue for osteoarthritis therapeutics.

Osteoarthritis is a common chronic arthritis among adults and cartilage dysfunction is largely responsible for osteoarthritis development.     

Long non-coding RNA DLX6-AS1/miR-141-3p axis regulates osteosarcoma proliferation,migration and invasion through regulating Rab10

Long non-coding RNA (lncRNAs) DLX6-AS1 plays significant roles in various types of malignant tumors, including osteosarcoma (OS), the most prevalent primary malignant bone tumor. However, the role and mechanism of DLX6-AS1 have not been fully illuminated in OS. Here, we aimed to find a novel mechanism for DLX6-AS1 in regulating the development of OS through sponging microRNA (miRNA). According to the luciferase reporter assay, RNA immunoprecipitation and RNA pull-down assay, miRNA (miR)-141-3p can physically interact with DLX6-AS1 and Rab10. The expressions of DLX6-AS1 and Rab10 were upregulated and miR-141-3p was downregulated in OS tissues and cells (MG-63 and U2OS), as described by RT-qPCR and western blotting. Moreover, there was a negative correlation between the expression of miR-141-3p and either DLX6-AS1 or Rab10, and a positive correlation between DLX6-AS1 and Rab10. Functionally, cell proliferation, migration and invasion were evaluated by utilizing the MTT assay and transwell assays. As a result, DLX6-AS1 knockdown suppressed OS cell proliferation, migration and invasion in MG-63 and U2OS cells, which was abolished by the downregulation of miR-141-3p. Similarly, the upregulation of Rab10 not only promoted OS cell progression in vitro, but also blocked the inhibitory effect of miR-141-3p overexpression in OS cells. Notably, DLX6-AS1 knockdown could, in turn, reverse the promoting effect of Rab10 on OS cell progression. Xenograft experiments depicted that DLX6-AS1 knockdown restrained the tumor growth of MG-63 cells in vivo. In conclusion, the knockdown of DLX6-AS1 might suppress OS progression via sponging miR-141-3p and downregulating Rab10, suggesting a novel DLX6-AS1/miR-141-3p/Rab10 pathway in OS progression.

Long non-coding RNA (lncRNAs) DLX6-AS1 plays significant roles in various types of malignant tumors, including osteosarcoma (OS), the most prevalent primary malignant bone tumor.