LncRNA HOTAIRM1 is involved in the progression of acute myeloid leukemia through targeting miR-148b

LncRNAs have been shown to be involved in the biological and pathological processes of acute myeloid leukemia (AML). Hox antisense intergenic RNA myeloid 1 (HOTAIRM1) was reported to be highly expressed in AML. However, the detailed role and molecular mechanism of HOTAIRM1 in AML pathogenesis remain undefined. In the present study, HOTAIRM1 and miR-148b expressions in AML patients and healthy controls were detected by qRT-PCR. Cell proliferation and apoptosis were evaluated by CCK-8 and flow cytometry assays, respectively. The regulatory interaction between HOTAIRM1 and miR-148b was explored by bioinformatics analysis using starBase v3.0 software and The Cancer Genome Atlas (TCGA) AML dataset. We found that the miR-148/miR-152 family members including miR-148a, miR-148b, and miR-152 were predicted to be potential targets of HOTAIRM1. HOTAIRM1 expression was negatively correlated with miR-148b expression but had no correlation with miR-148a/miR-152 expressions in AML samples from the TCGA dataset. HOTAIRM1 expression was higher while miR-148b expression was lower in AML patients than in healthy controls. A negative correlation between HOTAIRM1 and miR-148b in AML patients was observed. HOTAIRM1 silencing and miR-148b overexpression both suppressed cell proliferation and induced apoptosis in AML cells. miR-148b was identified as a target of HOTAIRM1 in AML cells. Moreover, HOTAIRM1 knockdown inhibited proliferation and induced apoptosis in AML cells by negatively regulating miR-148b. In summary, HOTAIRM1 was involved in the progression of AML through targeting miR-148b, shedding light on the biological function and molecular mechanism of HOTAIRM1 in AML.

LncRNAs have been shown to be involved in the biological and pathological processes of acute myeloid leukemia (AML).     

Knockdown of UCA1 inhibits viability and glycolysis by suppressing PKM2 expression through the mTOR pathway in non-small cell lung cancer cells

LncRNA urothelial carcinoma associated 1 (UCA1) was reported to be upregulated in non-small cell lung cancer (NSCLC) tissues and contributed to NSCLC progression. Additionally, it has been proposed that the oncogenic role of UCA1 may be related to glucose metabolism in bladder cancer. However, whether and how UCA1 regulates glucose metabolism in the progression of NSCLC remains unknown. Our results showed that knockdown of UCA1 inhibited the viability of NSCLC cells. UCA1 silencing suppressed glycolysis of NSCLC cells by reducing the glucose consumption and lactate production. Additionally, knockdown of UCA1 suppressed PKM2 expression and the mTOR pathway in NSCLC cells. Mechanistically, PKM2 knockdown suppressed the effects of UCA1 on viability and glycolysis of NSCLC cells and inhibition of the mTOR pathway suppressed the effects of UCA1 on viability, glycolysis, and PKM2 expression in NSCLC cells. In conclusion, knockdown of UCA1 inhibited viability and glycolysis by suppressing PKM2 expression maybe through the mTOR pathway in NSCLC cells, providing a novel insight into the molecular mechanism of UCA1 involved in the regulation of glucose metabolism in NSCLC cells.

LncRNA urothelial carcinoma associated 1 (UCA1) was reported to be upregulated in non-small cell lung cancer (NSCLC) tissues and contributed to NSCLC progression.     

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.     

LINC00115 regulates lung adenocarcinoma progression via sponging miR-154-3p to modulate Sp3 expression

The most commonly diagnosed and most lethal subtype of lung cancer is lung adenocarcinoma (LUAD). Therefore, more detailed understanding of the potential mechanism and identification of potential targets of lung adenocarcinoma is needed. A growing number of reports reveals that long non-coding RNAs (lncRNAs) play crucial roles in cancer progression. In present study, we found that lncRNA LINC00115 was upregulated in LUAD tissues and cells. Functional studies revealed that LINC00115 knockdown inhibits the proliferation, growth, invasion, and migration of LUAD cells. Mechanically, we indicated that miR-154-3p is target microRNA of LINC00115, and the effect of downregulated LINC00115 on LUAD cells was partially reversed by the miR-154-3p antisense oligonucleotide (ASO-miR-154-3p). Further investigation revealed that Specificity protein 3 (Sp3) directly interacted with miR-154-3p, and the Sp3 level was positively correlated with the LINC00115 expression. Rescue experiments further showed that Sp3 overexpression partially restored the effect of downregulated LINC00115 on LUAD cells. Similarly, in vivo experiments confirmed that downregulated LINC00115 inhibited xenograft growth and Sp3 expression. Our results demonstrated that LINC00115 knockdown inhibited LUAD progression via sponging miR-154-3p to modulate Sp3 expression. These data indicate that the LINC00115/miR-154-3p/Sp3 axis can be a potential therapeutic target of LUAD.     

Silencing of MicroRNA-21 confers the sensitivity to tamoxifen and fulvestrant by enhancing autophagic cell death through inhibition of the PI3K-AKT-mTOR pathway in breast cancer cells

Tamoxifen (TAM) and fulvestrant (FUL) represent the major adjuvant therapy to estrogen receptor-alpha positive (ER⁺) breast cancer patients. However, endocrine resistance to TAM and FUL is a great impediment for successful treatment. We hypothesized that miR-21 might alter the sensitivity of breast cancer cells to TAM or FUL by regulating cell autophagy. Using the ER⁺ breast cancer cells, we knockdown miR-21.by transfection with miR-21 inhibitor, then the cells were exposed to TAM or FUL and the percentages of apoptosis and autophagy were determined. Knockdown of miR-21 significantly increased the TAM or FUL-induced apoptosis in ER⁺ breast cancer cells. Further, silencing of miR-21 in MCF-7 cells enhanced cell autophagy at both basal and TAM or FUL-induced level. The increase of autophagy in miR-21-knockdown MCF-7 cells was also indicated by increase of beclin-1, LC3-II and increased GFP-LC3 dots. Importantly, knockdown of miR-21 contributed to autophagic cell death, which is responsible for part of TAM induced cell death in miR-21 inhibitor-transfected cells. Further analysis suggested that miR-21 inhibitor enhance autophagic cell death through inhibition of PI3K-AKT-mTOR pathway. MiR-21 coordinated the function of autophagy and apoptosis by targeting Phosphatase and tensin homolog (PTEN) through inhibition of PI3K-AKT-mTOR pathway. In conclusion, silencing of miR-21 increased the sensitivity of ER⁺ breast cancer cells to TAM or FUL by increasing autophagic cell death. Targeting autophagy-related miRNAs is a potential strategy for overcoming endocrine resistance to TAM and FUL.     

Small peptide LINC00511-133aa encoded by LINC00511 regulates breast cancer cell invasion and stemness through the Wnt/β-catenin pathway

LINC00511 is an long non-coding RNA (lncRNA) of ncRNAs,This study aimed to investigate whether the lncRNA LINC00511 could encode a small peptide, LINC00511-133aa, and whether this peptide could promote breast cancer cell metastasis and stemness by activating the wnt/β-catenin pathway. The LINC00511-133aa coding sequence vector and control vector were transfected into MCF-7 and MDA-MB-231 breast cancer cells, with subsequent assessment of peptide expression using PCR, western blotting, and immunofluorescence assays. Cell proliferation, invasion, and apoptosis were evaluated using CCK8, apoptotic, wound healing, and transwell invasion assays, while the characteristic changes of tumor stem cells were detected through sphere-forming assay and western blot analyses of the stemness markers Oct4, Nanog, and SOX2. Results showed that LINC00511-133aa was indeed encoded by LINC00511 and promoted the invasiveness and stemness of breast cancer cells while limiting apoptosis by modulating the expression levels of wnt/β-catenin pathway-related proteins Bax, c-myc, and CyclinD1, as well as facilitating β-catenin protein entry into the nucleus. This study provides evidence for the potential involvement of lncRNA LINC00511 and its peptide product in breast cancer progression via the regulation of the wnt/β-catenin pathway.     

Retracted Article: Exosomal miR-25-3p derived from hypoxia tumor mediates IL-6 secretion and stimulates cell viability and migration in breast cancer

Hypoxia is a major hallmark of solid tumors and is associated with malignant phenotypes. Exosomal miRNAs derived from hypoxia tumor cells are implicated in the modulation of cancer progression, whereas, the mechanisms underlying the association between hypoxia and exosomal miR-25-3p during breast cancer progression remain to be further clarified. The present study aimed to investigate the role of exosomal miR-25-3p in regulating breast cancer progression. Herein, we found that miR-25-3p expression was increased in hypoxia tumor-derived exosomes a HIF-1α-dependent manner. Hypoxia exosomes markedly stimulated the viability and migration of normoxia breast cancer cells, which was reversed by miR-25-3p depletion. Inhibition of exosomes miR-25-3p lowered hypoxic-induced the expression of IL-6 and NF-κB from THP-1 and RAW264.7 cells in a TLR7/8-dependent way. Treatment of macrophage supernatant (MS) initially incubated with hypoxic-responsed exosomes accelerated the viability and migration of breast cancer cells, and miR-25-3p depletion relieved the stimulatory effects of hypoxic on cell viability and migration. Moreover, miR-25-3p knockdown dramatically suppressed HIF-1α-induced tumor growth in vivo via inactivation of IL-6/STAT3 signaling pathway, reflected by the abated abundances of IL-6 and p-STAT3. These data suggested that absence of exosomal miR-25-3p rescued breast cancer aggressiveness through inhibiting cell viability and migration by regulation of IL-6 secretion from macrophages, providing a potential biomarker for breast cancer treatment.

Hypoxia is a major hallmark of solid tumors and is associated with malignant phenotypes.     

MiR-101在乳腺癌中的表达及其意义

目的:探讨miR-101在乳腺癌组织中的表达变化。方法:收集乳腺癌组织及对应的癌旁组织,以qRT-PCR方法测定miR-101在乳腺癌组织中的表达变化。在乳腺癌细胞中转染miR-101 mimics、mimics control,以qRT-PCR方法检测上调效果,MTT方法测定细胞增殖变化,流式细胞术测定细胞凋亡变化,Transwell小室测定细胞迁移和侵袭数目变化,蛋白质印迹法测定细胞中cleaved caspase-3和MMP-2蛋白表达变化。结果:miR-101在乳腺癌组织中的表达水平明显低于癌旁组织(P<0.05)。与miR-NC比较,miR-101细胞中miR-101表达水平升高,细胞增殖能力降低,细胞凋亡率升高,细胞侵袭和迁移数目下降,细胞内的cleaved caspase-3蛋白水平表达升高,MMP-2蛋白表达水平减少(P<0.05)。结论:MiR-101在乳腺癌组织中表达下调,上调miR-101抑制乳腺癌细胞增殖、侵袭和迁移并诱导细胞凋亡。     

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.     

miR-601 is a prognostic marker and suppresses cell growth and invasion by targeting PTP4A1 in breast cancer

MicroRNAs (miRNA) play important roles in the initiation and progression of breast cancer. Here, we investigated the role of miR-601 in breast cancer and found that its expression was significantly down-regulated in breast cancer tissues compared with matched adjacent non-cancerous breast tissues. Moreover, we found that down-regulation of miR-601 was closely associated with distant metastasis and poor distant metastasis-free survival in breast cancer. In addition, miR-601 levels were inversely correlated with metastatic potential of human breast cancer cell lines. Further experiments showed that ectopic overexpression of miR-601 suppressed breast cancer cell proliferation, migration and invasion, whereas miR-601 knockdown promoted breast cancer cell proliferation, migration and invasion. Furthermore, protein tyrosine phosphatase type IVA 1 (PTP4A1) was identified as a direct target of miR-601. Overexpression of miR-601 repressed PTP4A1 mRNA and protein expression. Conversely, inhibition of miR-601 increased PTP4A1 mRNA and protein expression. Taken together, our data suggest that miR-601 inhibits growth and invasion of breast cancer cells by targeting PTP4A1 and that miR-601 is a potential biomarker for prognosis and therapeutic target in breast cancer.     

Retracted Article: Linc00472 suppresses breast cancer progression and enhances doxorubicin sensitivity through regulation of miR-141 and programmed cell death 4

The existence of drug resistance strikingly hampers the therapy of many malignancies, including breast cancer. Long non-coding RNAs (LncRNAs) have been reported to participate in the regulation of various biological processes associated with cancer progression. Whereas, the role of linc00472 in breast cancer pathogenesis and doxorubicin (ADR) resistance have not been well elucidated. In the present study, it is found that linc00472 expression was decreased in breast cancer tissues and cells. Moreover, higher linc00472 expression was positively associated with favorable disease status and prognosis for breast cancer patients. Functional analyses revealed that linc00472 overexpression suppressed proliferation and invasion, facilitated apoptosis and enhanced ADR sensitivity in breast cancer cells. Mechanistic studies discovered that linc00472 acted as a competing endogenous RNA (ceRNA) of miR-141 to sequester miR-141 from its target mRNA PDCD4 (programmed cell death 4). Furthermore, the inhibition effect of linc00472 on breast cancer cell progression and ADR resistance could be partly abrogated by miR-141 up-regulation or PDCD4 knockdown. In vivo assays also demonstrated that linc00472 hindered tumor growth by suppressing miR-141 expression and enhancing PDCD4 expression. In conclusion, linc00472 blocked breast cancer progression and induced ADR sensitivity through regulation of miR-141 and PDCD4, highlighting a potential therapeutic strategy for breast cancer patients.

Linc00472 expression was down-regulated in breast cancer tissues and cells, and was associated with the development and prognosis of breast cancer.     

LncRNA LINC00210 regulated radiosensitivity of osteosarcoma cells via miR-342-3p/GFRA1 axis

BackgroundRadiotherapy is an effective strategy for preventing cancer metastasis, including osteosarcoma. However, cancer radioresistance limits the efficiency of radiotherapy. Therefore, it is essential to investigate the mechanism of osteosarcoma radioresistance.MethodsThe osteosarcoma tissues and adjacent healthy tissues were collected from 53 osteosarcoma patients. The expression of LINC00210, miR‐342‐3p, and GFRA1 mRNA were determined using qRT‐PCR. Cell viability, cell apoptosis, and cell surviving fraction were determined by MTT assay, flow cytometry, and colony formation assay, respectively. Western blot was performed to detect the protein levels. Luciferase assay was conducted to verify the relationship between LINC00210, miR‐342‐3p, and GFRA1.ResultsLINC00210 and GFRA1 were up‐regulated, and miR‐342‐3p was down‐regulated in osteosarcoma tissues and cells. The expression of LINC00210 in osteosarcoma was negatively related to miR‐342‐3p expression and positively associated with GFRA1. Besides, there was a negative correlation between LINC00210 and GFRA1 expression in osteosarcoma. Also, LINC00210 and GFRA1 were up‐regulated, and miR‐342‐3p was down‐regulated in osteosarcoma cells exposed to 4 Gy irradiation treatment. Furthermore, either LINC00210 knockdown or miR‐342‐3p overexpression enhanced the radiosensitivity of osteosarcoma cells. Moreover, LINC00210 increased GFRA1 expression via sponging miR‐342‐3p. Additionally, LINC00210 knockdown improved the radiosensitivity of osteosarcoma cells by regulating GFRA1 expression via sponging miR‐342‐3p.ConclusionLINC00210 modulated the radiosensitivity of osteosarcoma cells via the miR‐342‐3p/GFRA1 axis, making LINC00210 a novel target for improving radiotherapy efficiency in osteosarcoma.     

Gas5 Exerts Tumor-suppressive Functions in Human Glioma Cells by Targeting miR-222

Aberrant expression of noncoding RNAs in glioma cells, including long noncoding RNAs (lncRNAs) and microRNAs, may participate in the progression of glioma. Encoded by Growth Arrest-Specific 5 (GAS5) gene, lncRNA Gas5 was reported to be a negative regulator for survival and proliferation of several cancers. Here, Gas5 is found to be downregulated in glioma specimens and U87 and U251 glioma cell lines. We showed that the introduction of Gas5 by plasmid transfection increased the expression of tumor suppressor Bcl-2-modifying factor (bmf) and Plexin C1 via directly targeting and reducing the expression of miR-222. Downregulated expression of miR-222 inhibited U87 and U251 cell proliferation and promoted the apoptosis by upregulating bmf. As downstream signaling molecules of bmf, Bcl-2 and Bax were involved in the process. Meanwhile, knockdown of miR-222 attenuated U87 and U251 cell migration and invasion by upregulating Plexin C1, and cofilin was a crucial regulator targeted by Plexin C1. Gas5 combined with the knockdown of miR-222 resulted in the smallest tumor volumes and the longest survivals of nude mice in vivo. In summary, we show that Gas5 suppresses tumor malignancy by downregulating miR-222, which may serve as a promising therapy for glioma.     

LINC01224靶向miR-125b对口腔鳞癌细胞增殖及凋亡的影响

摘要：目的?探讨长链非编码RNA(LncRNA)LINC01224是否通过调控微小RNA-125b(miR-125b)的表达，从而影响口腔鳞癌(OSCC)细胞增殖及凋亡。方法?采用实时荧光定量聚合酶链反应(qRT-PCR)检测OSCC患者癌组织及癌旁组织中LINC01224的表达水平；体外培养OSCC细胞系CAL-27，将si-NC、si-LINC01224、si-LINC01224与anti-miR-NC、si-LINC01224与anti-miR-125b转染至CAL-27细胞；甲基噻唑基四唑(MTT)试验检测细胞增殖能力；流式细胞术检测细胞周期与细胞凋亡率；双荧光素酶报告试验验证LINC01224与miR-125b的靶向结合关系；western blot检测半胱氨酰天冬氨酸特异性蛋白酶3前体蛋白(pro-caspase-3)、增殖标记蛋白细胞增殖核抗原67(Ki67)、活化的含半胱氨酸的天冬氨酸蛋白水解酶3(clv-caspase-3)、P21蛋白的表达水平。结果?与癌旁组织相比，OSCC患者癌组织中LINC01224的表达水平(1.00±0.05 vs 2.43±0.17)显著升高(t=94.345，P<0.05)，miR-125b的表达水平(0.98±0.06 vs 0.22±0.02)显著降低(t=14.838，P<0.05)；与si-NC组比较，si-LINC01224组细胞存活率[(100.02±6.73)% vs (47.94±4.69)%]显著降低(t=19.047，P<0.05)，G1期细胞比例[(31.03±3.01)% vs (42.29±4.12)%]显著增加(t=6.615，P<0.05)，S期细胞比例[(34.18±3.38)% vs (23.49±2.57)%]显著减少(t=7.553，P<0.05)，细胞凋亡率[(8.10±0.92)% vs (24.17±1.74)%]显著升高(t=24.494，P<0.05)，Ki67、pro-caspase-3蛋白水平显著降低(P<0.05)，P21、clv-caspase-3蛋白水平显著升高(P<0.05)；双荧光素酶报告试验证实LINC01224与miR-125b靶向结合；与si-LINC01224+anti-miR-NC组比较，si-LINC01224+anti-miR-125b组细胞存活率[(48.03±4.57)% vs (90.01±5.59)%]显著升高(t=17.442，P<0.05)，细胞凋亡率[(24.11±1.58)% vs (12.81±1.12)%]显著降低(t=17.504，P<0.05)，G1期细胞比例[(42.27±4.10)% vs (35.09±3.18)%]显著减少(t=4.151，P<0.05)，S期细胞比例[(23.53±2.54)% vs (30.03±2.96)%]显著增加(t=4.999，P<0.05)，pro-caspase-3、Ki67蛋白水平显著升高(P<0.05)，clv-caspase-3、P21蛋白水平显著降低(P<0.05)。结论?LINC01224能够靶向调控miR-125b的表达，从而促进OSCC细胞增殖及抑制细胞凋亡。     

Dihydroartemisinin induces apoptosis and downregulates glucose metabolism in JF-305 pancreatic cancer cells

Cancer cell promotion of glycolysis provides a promising therapeutic target for cancer treatment. Dihydroartemisinin (DHA) displays cytotoxicity to multiple human tumor cells. However, its effects on pancreatic cancer cells are not well studied. The objective of this study was to investigate the effect of DHA on glucose metabolism and cell viability in JF-305 pancreatic cancer cells. To achieve these goals, cell viability was measured with MTT assay, and the occurrence of apoptosis was detected. Glucose uptake, lactate production, and ATP content were measured. Western blotting was used for the detection of apoptosis-related protein expression. The result showed that DHA caused significant reduction in JF-305 cell viability, arrested the cell phase in G₂/M, induced apoptosis, and decreased the mitochondrial membrane potential and accumulated ROS. DHA also inhibited glucose uptake, lactate generation, and ATP production. Western blotting showed that treatment with DHA increased the activity of caspase-9 and caspase-3, downregulated Bcl-2 expression, and upregulated the expression levels of Bax and Cyto C. Meanwhile, DHA downregulated the Akt/mTOR signaling pathway and inhibited glucose transporter 1 expression. Our data suggest that DHA treatment increased the apoptosis of JF-305 pancreatic cancer cells, and the effect of apoptosis may be associated with the inhibition of glycolysis.

Cancer cell promotion of glycolysis provides a promising therapeutic target for cancer treatment.     

Retracted Article: Gemcitabine aggravates miR-199a-5p-mediated breast cancer cell apoptosis by promoting VEGFA downregulation via inactivating the AKT signaling pathway

Breast cancer is the most frequent malignancy diagnosed in women, and Gemcitabine-based therapy is frequently used to treat late-stage breast cancer. miR-199a-5p plays a tumor-suppressive role in breast cancer. This work aimed to explore the mechanism of miR-199a-5p plus Gemcitabine in breast cancer cells. Expression of miR-199a-5p was measured by RT-qPCR, while expression of vascular endothelial growth factor A (VEGFA) was measured by Western blot and RT-qPCR. Overexpression of miR-199a-5p and/or silencing of VEGFA was obtained using transfection in breast cancer cells (MCF-7 and MDA-MB-231). Functional experiments were performed to explore cell viability, apoptosis rate, and expressions of apoptosis-related genes: cell viability was assessed by MTT staining, apoptosis rate was recorded by flow cytometry, and Western blot was used to evaluate the expressions of Bcl-2, Bax and cleaved caspase 3. The signaling pathway was studied with respect to AKT activity via determination of p-AKT expression levels. Our study found that miR-199a-5p was downregulated and VEGFA was upregulated in breast cancer tissues and cells. Overexpression of miR-199a-5p and/or silencing of VEGFA contributed to cell apoptosis and inhibited cell viability, which was promoted by Gemcitabine. VEGFA was a downstream target of miR-199a-5p, and was negatively regulated by Gemcitabine. Moreover, Gemcitabine aggravated the miR-199a-5p-induced suppression of the VEGFA level and AKT activity in breast cancer cells. Our data show that Gemcitabine aggravates miR-199a-5p-mediated VEGFA downregulation and apoptosis via inactivating the AKT signaling pathway in breast cancer cells, indicating a novel promising combined therapy of miR-199a-5p overexpression and Gemcitabine.

Breast cancer is the most frequent malignancy diagnosed in women, and Gemcitabine-based therapy is frequently used to treat late-stage breast cancer.     

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.