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doi:10.18632/oncotarget.v6i26

Cited by 8 publications

(7 citation statements)

References 4 publications

(4 reference statements)

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“…29 Similarly, in another study, FBXO22 was also found to promote the progression of hepatocellular carcinoma by regulating the ubiquitination and degradation of KLF4. 30 At present, there is no research report on the relationship between circ_0006282, miR-155 and FBXO22. In this study, we demonstrated that circ_0006282 promotes FBXO22 expression and gastric cancer progression through sponging miR-155.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circ_0006282 Contributes to the Progression of Gastric Cancer by Sponging miR-155 to Upregulate the Expression of FBXO22

He¹,

Wang²,

Liu³

et al. 2020

OTT

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Background: There is increasing evidence that circular RNAs (circRNAs) play an important role in human cancers. As a newly identified human circular RNA, circ_0006282 is abnormally expressed in several types of cancers and promotes the development of cancers. However, the expression and function of circ_0006282 in gastric cancer (GC) remain unclear. Methods: The expression of circ_0006282 in cancer tissues and adjacent non-cancer tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR) method, and the relationship between circ_0006282 expression and clinicopathological parameters was analyzed. After knockdown of circ_0006282 by RNA interference in GC cells, CCK-8 assay, colony formation and transwell assays were conducted to examine the effects of circ_0006282 on GC cells. The influence of circ_0006282 on tumor growth in vivo was assessed in a xenograft model. Furthermore, regulatory relationship between circ_0006282, miR-155 and FBXO22 was detected by luciferase assay, qRT-PCR and Western blot. Results: The expression of circ_0006282 in GC tissues was significantly higher than its adjacent non-cancer tissues and over-expression of circ_0006282 was associated with tumor size, lymph nodes metastasis and TNM stage, but no obvious links with other pathological parameters. Knockdown of circ_0006282 inhibited the proliferation and metastasis ability of GC cells in vitro and suppressed the tumor growth in vivo. Furthermore, mechanistic investigations suggested that circ_0006282 served as a competing endogenous RNA (ceRNA) of miR-155. Moreover, FBXO22 was identified as the functional target of miR-155 and down-expression of circ_0006282 inhibited FBXO22 expression. Rescue assays also demonstrated that the oncogenic function of circ_0006282 is partly attributed to its regulation on miR-155/FBXO22 axis. Conclusion: Our findings indicated that over-expression of circ_0006282 down-regulated miR-155 to activate the expression of FBXO22, thus promoting proliferation and metastasis of GC cells, which provides a promising therapeutic target for GC treatment.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circ_0006282 Contributes to the Progression of Gastric Cancer by Sponging miR-155 to Upregulate the Expression of FBXO22

He¹,

Wang²,

Liu³

et al. 2020

OTT

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“…29 RAB3D was also discovered to promote the CDK4 and CDK6 signaling, thereby stimulating cell cycle progression and ultimately leading to the proliferation of tumor cells. 30,31 In our future research, we will work to study the effects of RAB3D on NSCLCassociated classical signaling pathways. Of course, there are limitations to this research.…”

Section: Discussionmentioning

confidence: 99%

CircRNA hsa_circ_0087862 Acts as an Oncogene in Non-Small Cell Lung Cancer by Targeting miR-1253/RAB3D Axis

Wan

Xiong

et al. 2020

OTT

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Purpose: Circular RNAs (circRNAs) have been found to regulate several human tumors. The present study was to explore the mechanism of hsa_circ_0087862 in regulating nonsmall cell lung cancer (NSCLC). Methods: Totally 102 NSCLC cases were enrolled. NCI-H1359 and A549 cells were transfected. Cells viability, apoptosis, migration and invasion were determined by CCK-8 assay, flow cytometry, scratch test and transwell experiment, respectively. Luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were performed. Xenograft tumor experiments were performed using nude mice. hsa_circ_0087862, miR-1253 and RAB3D expression in tissues/cells were detected by qRT-PCR. RAB3D and Ki67 protein expressions in cells/tissues were researched by Western blot and immunohistochemistry. Apoptosis of xenograft tumor tissue cells was detected using Tunel assay. Results: hsa_circ_0087862 was significantly up-regulated in NSCLC patients, which was associated with poor prognosis (P < 0.05). hsa_circ_0087862 down-regulation prominently weakened NSCLC cells viability, migration, invasion and enhanced apoptosis (P < 0.01). hsa_circ_0087862 overexpression exhibited the opposite results in NSCLC cells. miR-1253 was sponged by hsa_circ_0087862. miR-1253 expression in NSCLC tissues was negatively correlated with hsa_circ_0087862 (P < 0.001). RAB3D expression in NSCLC was directly inhibited by miR-1253. miR-1253 down-regulation or RAB3D overexpression dramatically reversed NSCLC cells phenotype induced by hsa_circ_0087862 down-regulation. hsa_circ_0087862 down-regulation markedly inhibited tumor growth in vivo (P < 0.01). In xenograft tumor tissues, hsa_circ_0087862 down-regulation obviously decreased expression of RAB3D, Ki67 and increased apoptosis. Conclusion: hsa_circ_0087862 acted as an oncogene in NSCLC by targeting miR-1253/ RAB3D.

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“…It uses a pH-sensitive, cleavable linker designed to impart cytotoxic activity to both target and bystander cells via ADC internalization and local release of the free drug at the tumor. 25,26 In this work, we redesigned anti-CD30-vcMMAE (ADCETRIS) to make it safer in the blood system by conjugating the antibody to DM1 through a noncleavable peptide linker to create anti-CD30-MCC-DM1. Both MMAE and DM1 belong to the class of tubulin inhibitors, and with free drug IC 50 values between 10 −11 and 10 −9 , they have been used successfully in commercialized ADCs.…”

Section: Discussionmentioning

confidence: 99%

Conjugation of DM1 to anti-CD30 antibody has potential antitumor activity in CD30-positive hematological malignancies with lower systemic toxicity

Shen

Tong²,

Cao³

et al. 2019

mAbs

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An anti-CD30 antibody-drug conjugate incorporating the antimitotic agent DM1 and a stable SMCC linker, anti-CD30-MCC-DM1, was generated as a new antitumor drug candidate for CD30-positive hematological malignancies. Here, the in vitro and in vivo pharmacologic activities of anti-CD30-MCC-DM1 (also known as F0002-ADC) were evaluated and compared with ADCETRIS (brentuximab vedotin). Pharmacokinetics (PK) and the safety profiles in cynomolgus monkeys were assessed. Anti-CD30-MCC-DM1 was effective in in vitro cell death assays using CD30-positive lymphoma cell lines. We studied the properties of anti-CD30-MCC-DM1, including binding, internalization, drug release and actions. Unlike ADCETRIS, anti-CD30-MCC-DM1 did not cause a bystander effect in this study. In vivo, anti-CD30-MCC-DM1 was found to be capable of inducing tumor regression in subcutaneous inoculation of Karpas 299 (anaplastic large cell lymphoma), HH (cutaneous T-cell lymphoma) and L428 (Hodgkin’s disease) cell models. The half-lives of 4 mg/kg and 12 mg/kg anti-CD30-MCC-DM1 were about 5 days in cynomolgus monkeys, and the tolerated dose was 30 mg/kg in non-human primates, supporting the tolerance of anti-CD30-MCC-DM1 in humans. These results suggest that anti-CD30-MCC-DM1 presents efficacy, safety and PK profiles that support its use as a valuable treatment for CD30-positive hematological malignancies.

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Untitled

Cited by 8 publications

References 4 publications

<p>Circular RNA circ_0006282 Contributes to the Progression of Gastric Cancer by Sponging miR-155 to Upregulate the Expression of FBXO22</p>

<p>Circular RNA circ_0006282 Contributes to the Progression of Gastric Cancer by Sponging miR-155 to Upregulate the Expression of FBXO22</p>

<p>CircRNA hsa_circ_0087862 Acts as an Oncogene in Non-Small Cell Lung Cancer by Targeting miR-1253/RAB3D Axis</p>

Conjugation of DM1 to anti-CD30 antibody has potential antitumor activity in CD30-positive hematological malignancies with lower systemic toxicity

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