Abstract:
:Deletion and mutation of the Smad4 gene are favorable events for the progression of colon cancer, which is related to the negative regulation of vascular endothelial growth factor C (VEGF-C). However, the regulatory mechanism between Smad4 and VEGF-C remains unclear. We reported first that Smad4 can increase the transcription of miR-128-3p, a microRNA targeting VEGF-C mRNA, resulting in a negative correlation between Smad4 and VEGF-C. Moreover, we found that Smad4 combined with Smad3 can positively regulate VEGF-C during colon cancer metastasis through binding to VEGF-C gene promoter. Further, results revealed a mechanism that long noncoding RNA (lncRNA) ASLNC07322 increased specifically in metastatic colon cancer and decreased miR-128-3p as a sponge, leading to a subsequent elevation of VEGF-C. In a word, there are two pathways in the progression of colon cancer, including Smad4/miR-128-3p/VEGF-C and Smad4/VEGF-C pathways in non-metastatic and metastatic colon cancer, respectively. ASLNC07322 crucially controlled this negative and positive regulatory transformation between them. Additionally, ASLNC07322 knockdown combined with Smad4 overexpression could efficiently inhibit lymphatic endothelial cells (LECs) proliferation and tube formation in vitro, as well as tumor growth and lymphangiogenesis in vivo. These data explained the underlying mechanism of Smad4 contribution on VEGF-C expression during metastasis where ASLNC07322 functions vitally as a switch in colon cancer.
journal_name
Mol Ther Nucleic Acidsjournal_title
Molecular therapy. Nucleic acidsauthors
Li X,Lv X,Li Z,Li C,Li X,Xiao J,Liu B,Yang H,Zhang Ydoi
10.1016/j.omtn.2019.10.012subject
Has Abstractpub_date
2019-12-06 00:00:00pages
851-862issn
2162-2531pii
S2162-2531(19)30309-9journal_volume
18pub_type
杂志文章abstract::Breast cancer, as the most common cancer in women worldwide, represents about 30% of all cancers affecting women. Long non-coding RNAs (lncRNAs) have been implicated in the regulation of several biological processes, and their dysregulation in cancer has well been documented. To investigate possible age-dependent vari...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.07.014
更新日期:2018-09-07 00:00:00
abstract::Numerous studies have suggested that dysregulated long noncoding RNAs (lncRNAs) contributed to the development and progression of many cancers. lncRNA OIP5 antisense RNA 1 (OIP5-AS1) has been reported to be increased in several cancers. However, the roles of OIP5-AS1 in liver hepatocellular carcinoma (LIHC) remain to ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.05.032
更新日期:2020-09-04 00:00:00
abstract::We previously found that inhibition of p66Shc confers protection against hepatic stellate cell (HSC) activation during liver fibrosis. However, the effect of p66Shc on HSC proliferation, as well as the mechanism by which p66Shc is modulated, remains unknown. Here, we elucidated the effect of p66Shc on HSC proliferatio...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.07.013
更新日期:2020-09-04 00:00:00
abstract::Due to highly enzymatic d-stereoselectivity, l-nucleotides (l-2'-deoxynucleoside 5'-triphosphates [l-dNTPs]) are not natural targets of polymerases. In this study, we synthesized series of l-thymidine (l-T)-modified DNA strands and evaluated the processivity of nucleotide incorporation for transcription by T7 RNA poly...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.06.023
更新日期:2020-09-04 00:00:00
abstract::Keratinocyte proliferation and migration are crucial steps during skin wound healing. The functional role of microRNAs (miRs) remains relatively unknown during this process. miR-93 levels have been reported to increase within 24 h of skin wound healing; however, whether miR-93-3p or miR-93-5p plays a specific role in ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.11.017
更新日期:2020-11-26 00:00:00
abstract::Ribozyme genes were designed to reduce voluntary alcohol drinking in a rat model of alcohol dependence. Acetaldehyde generated from alcohol in the liver is metabolized by the mitochondrial aldehyde dehydrogenase (ALDH2) such that diminishing ALDH2 activity leads to the aversive effects of blood acetaldehyde upon alcoh...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2016.41
更新日期:2016-07-12 00:00:00
abstract::miR-221 is overexpressed in several malignancies where it promotes tumor growth and survival by interfering with gene transcripts, including p27Kip1, PUMA, PTEN, and p57Kip2. We previously demonstrated that a novel 13-mer miR-221 inhibitor (locked nucleic acid [LNA]-i-miR-221) exerts antitumor activity against human c...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.01.036
更新日期:2020-06-05 00:00:00
abstract::Long noncoding RNAs (lncRNAs), which serve as important and powerful regulators of various biological activities, have gained widespread attention in recent years. Emerging evidence has shown that some lncRNAs play important regulatory roles in osteoblast differentiation of mesenchymal stem cells (MSCs), suggesting a ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.03.004
更新日期:2018-06-01 00:00:00
abstract::Menin displays either tumor suppression or promotion functions in a context-dependent manner. Previously, we proposed that Menin acts as a tumor suppressor by inhibiting cell growth in pancreatic ductal adenocarcinoma (PDAC), whereas the relationship between the Menin expression and overall survival rate of PDAC patie...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.08.013
更新日期:2019-12-06 00:00:00
abstract::Hepatocellular carcinoma (HCC) has high fatality rate and limited therapeutic options. Here, we propose a new anti-HCC approach with high cancer-selectivity and efficient anticancer effects, based on adenovirus-mediated Tetrahymena group I trans-splicing ribozymes specifically inducing targeted suicide gene activity t...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.10.036
更新日期:2020-10-31 00:00:00
abstract::Targeted transcriptional modulation in the central nervous system (CNS) can be achieved by adeno-associated virus (AAV) delivery of CRISPR activation (CRISPRa) and interference (CRISPRi) transgenes. To enable AAV packaging, we constructed minimal CRISPRa and CRISPRi transgenes by fusing catalytically inactive Staphylo...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.04.015
更新日期:2019-06-07 00:00:00
abstract::Diabetic retinopathy (DR) is a serious complication of diabetes, which is the main cause of blindness among adults. Traditional Chinese medicines (TCMs) have been proven to delay the development of DR. Nonetheless, the effect of Schizandrin A (SchA) on DR remains uninvestigated. The present study aimed to probe the pr...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.10.026
更新日期:2020-03-06 00:00:00
abstract::Blocking the immunoinhibitory PD-1:PD-L1 pathway using monoclonal antibodies has led to dramatic clinical responses by reversing tumor immune evasion and provoking robust and durable antitumor responses. Anti-PD-1 antibodies have now been approved for the treatment of melanoma, and are being clinically tested in a num...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2015.11
更新日期:2015-04-28 00:00:00
abstract::Polycystic ovary syndrome (PCOS), characterized by the dysfunction of endocrine metabolism, is a common disease among women. Insulin (INS) resistance (IR) is considered as an obstruction to effective PCOS treatment. Here, we aimed to explore the mechanism by which microRNA-222 (miR-222) affects IR in PCOS via Pten. Qu...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.07.014
更新日期:2020-07-10 00:00:00
abstract::Inflammatory mediators play a key role in the pathogenesis of acute respiratory distress syndrome (ARDS). In this study, we aimed to explore the involvement of the Kcnq1 opposite strand/antisense transcript 1 (Kcnq1ot1)/miR-381-3p/E26 transformation-specific proto-oncogene 2 (ETS2) axis in inflammation of lipopolysacc...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.10.036
更新日期:2020-03-06 00:00:00
abstract::PCTAIRE1/CDK16/PCTK1 plays critical roles in cancer cell proliferation and antiapoptosis. To advance our previously published in vitro results with PCTAIRE1 silencing, we examined the in vivo therapeutic potential of this approach by using small interfering RNA (siRNA) encapsulated by lipid nanoparticles. Therapy expe...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2016.40
更新日期:2016-06-28 00:00:00
abstract::The role of microglia in the pathophysiology of ischemic retinal diseases has been studied extensively. Exosomes from microglial cells exert protective effects during several nervous system diseases, but their roles in hypoxia-induced retinopathy remain unclear. In our study, exosomes derived from microglial cells wer...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.04.029
更新日期:2019-06-07 00:00:00
abstract::The transforming growth factor-β (TGF-β)/Smads signal plays an important role in cancer metastasis by mediating the epithelial-mesenchymal transition (EMT) in cancer cells. lnc-TSI is a recently identified long noncoding RNA that negatively regulates the TGF-β/Smads signal. The present study was conducted to test the ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.08.003
更新日期:2020-08-05 00:00:00
abstract::Highly active antiretroviral therapy (HAART) has significantly improved the quality of life and the life expectancy of HIV-infected individuals. Still, drug-induced side effects and emergence of drug-resistant viral variants remain important issues that justify the exploration of alternative therapeutic options. One s...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2013.48
更新日期:2013-09-03 00:00:00
abstract::Cardiac hypertrophy, a response of the heart to increased workload, is a major risk factor for heart failure. Myostatin (MSTN) is an inhibitor of myogenesis, regulating the number and size of skeletal myocytes. In recent years, cardiomyocyte autophagy also has been considered to be involved in controlling the hypertro...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.12.003
更新日期:2020-03-06 00:00:00
abstract::Recent studies have suggested that microRNA let-7i is a tumor suppressor in human cancers, including esophageal cancer, but its underlying mechanism is not yet fully understood. We investigated the role and mechanisms of let-7i in the progression of esophageal cancer. We first showed that let-7i was downregulated in e...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.09.012
更新日期:2020-09-16 00:00:00
abstract::A number of studies have reported that aberrant expression of microRNAs (miRNAs) closely correlates with the bone metastasis of prostate cancer (PCa). However, clinical significance and functional roles of both strands of a single miRNA in bone metastasis of PCa remain undefined. Here, we reported that miR-582-3p and ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.01.004
更新日期:2019-06-07 00:00:00
abstract::Cardiomyocyte differentiation derived from embryonic stem cells (ESCs) is a complex process involving molecular regulation of multiple levels. In this study, we first identify and compare differentially expressed gene (DEG) signatures of ESC-derived cardiomyocyte differentiation (ESCDCD) in humans and mice. Then, the ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.07.011
更新日期:2020-09-04 00:00:00
abstract::The knockdown of myostatin, a negative regulator of skeletal muscle mass may have important implications in disease conditions accompanied by muscle mass loss like cancer, HIV/AIDS, sarcopenia, muscle atrophy, and Duchenne muscular dystrophy (DMD). In DMD patients, where major muscle loss has occurred due to a lack of...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2012.54
更新日期:2012-12-18 00:00:00
abstract::The ability to selectively target disease-related tissues with molecules is critical to the design of effective therapeutic and diagnostic reagents. Recognizing the differences between the in vivo environment and in vitro conditions, we employed an in vivo selection strategy to identify RNA aptamers (targeting motifs)...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2016.27
更新日期:2016-04-26 00:00:00
abstract::The microRNA(miRNA)-34a is a key regulator of tumor suppression. It controls the expression of a plethora of target proteins involved in cell cycle, differentiation and apoptosis, and antagonizes processes that are necessary for basic cancer cell viability as well as cancer stemness, metastasis, and chemoresistance. I...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章,评审
doi:10.1038/mtna.2014.47
更新日期:2014-09-23 00:00:00
abstract::In this study, chemical modification of 2'-deoxyinosine (2'-dI) and D-/L-isothymidine (D-/L-isoT) was performed on AS1411. They could promote the nucleotide-protein interaction by changing the local conformation. Twenty modified sequences were obtained, FCL-I and FCL-II showed the most noticeable activity improvement....
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2017.09.010
更新日期:2017-12-15 00:00:00
abstract::Antisense oligonucleotides complementary to RNA targets promise generality and ease of drug design. The first systemically administered antisense drug was recently approved for treatment and others are in clinical development. Chemical modifications that increase the hybridization affinity of oligonucleotides are reas...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2013.72
更新日期:2014-02-18 00:00:00
abstract::Bone marrow-derived mesenchymal stem cells (BMSCs) have been suggested to possess the capacity to differentiate into different cell lineages. Maintaining a balanced stem cell differentiation program is crucial to the bone microenvironment and bone development. MicroRNAs (miRNAs) have played a critical role in regulati...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.06.023
更新日期:2019-09-06 00:00:00
abstract::Osteoporosis is characterized by the reduction of bone mineral density and deterioration of bone quality which leads to high risk of fractures. Some microRNAs (miRNAs) have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass maintenance. We aimed to clarify whether miR-122 could ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.11.038
更新日期:2020-06-05 00:00:00