MicroRNAs in Pancreatic Cancer

胰腺癌中的 MicroRNA

基本信息

  • 批准号:
    7896664
  • 负责人:
  • 金额:
    $ 7.42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-07-20 至 2012-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Pancreatic cancer is a highly lethal malignancy with an extremely poor prognosis. A wide variety of biochemical and genetic aberrations have been identified to be associated with the pancreatic cancer. MUC4, encoding for a transmembrane mucin protein, is among the most differentially-expressed genes in pancreatic adenocarcinoma with no detectable expression in the normal pancreas. It is overexpressed in a significant number of pancreatic carcinomas, and its neoexpression is observed early in pancreatic tumor development i.e., in precancerous lesions. MUC4 has been shown to interact with and stabilize the expression of HER2 oncoprotein and contains structural motifs that can putatively interact with extracellular matrix, membrane and cytoplasmic proteins. MUC4 potentiates tumor growth and metastasis of pancreatic cancer cells and a recent study have shown that it is an independent factor for poor prognosis. All these studies underscore the importance of identifying the molecular mechanisms involved in the aberrant expression of MUC4, so that, it can be exploited clinically for therapeutic purposes. A new class of gene regulatory RNAs, termed as microRNAs (miRNAs) has gained significant interest for their ability to influence various biological process. A large number of miRNAs has been identified in humans. Nevertheless, the target mRNAs have been assigned to only a few of them. The hypothesis of this proposal is that the aberrant expression of a certain class of microRNAs in pancreatic cancer is responsible for MUC4 dysregulation and is implicated in the malignant progression of pancreatic cancer cells. This proposal will initiate efforts in three specific aims on investigating the expression profile of candidate MUC4-targeted miRNAs in pancreatic cancer (Aim 1), studying their role in MUC4 regulation (Aim 2), and characterize their effect on pancreatic cancer phenotype (Aim 3). Taken together, the proposed studies will unfold a novel regulatory mechanism for MUC4 expression in pancreatic cancer cells and ascribe the functional significance to the MUC4-targeted miRNAs in pancreatic cancer progression. The information gained from these studies will be vital in supporting the design of miRNA-based therapeutic strategies and clinical assays in pancreatic cancer. PUBLIC HEALTH RELEVANCE: The proposal will investigate the expression and functional significance of the candidate MUC4-targeted miRNAs in pancreatic cancer and may provide important information to support the design of miRNA-based therapeutic strategies and clinical assays for pancreatic cancer.
描述(由申请人提供):胰腺癌是一种高度致命的恶性肿瘤,预后极差。各种各样的生化和遗传畸变已被确定为与胰腺癌相关。MUC4编码跨膜粘蛋白,是胰腺癌中最差异表达的基因之一,在正常胰腺中未检测到表达。它在大量胰腺癌中过表达,并且在胰腺肿瘤发展的早期观察到其新表达,即,在癌前病变中。MUC4已被证明与HER2癌蛋白相互作用并稳定HER2癌蛋白的表达,并且含有可与细胞外基质、膜和细胞质蛋白相互作用的结构基序。MUC4促进胰腺癌细胞的生长和转移,最近的研究表明它是预后不良的独立因素。所有这些研究都强调了确定MUC4异常表达的分子机制的重要性,因此,它可以用于临床治疗目的。一类新的基因调控RNA(microRNA,miRNAs)因其能够影响多种生物学过程而引起人们的极大兴趣。已经在人类中鉴定了大量的miRNAs。然而,靶mRNA仅被分配给其中的少数。该提议的假设是,胰腺癌中某类microRNA的异常表达是MUC4失调的原因,并且与胰腺癌细胞的恶性进展有关。该提案将在三个具体目标上开展工作,即研究候选MUC4靶向miRNA在胰腺癌中的表达谱(目标1),研究它们在MUC4调节中的作用(目标2),以及表征它们对胰腺癌表型的影响(目标3)。综上所述,拟议的研究将揭示胰腺癌细胞中MUC4表达的新调控机制,并将胰腺癌进展中MUC4靶向miRNA的功能意义归因于MUC4。从这些研究中获得的信息对于支持胰腺癌中基于miRNA的治疗策略和临床测定的设计至关重要。公共卫生关系:该提案将研究候选MUC4靶向miRNA在胰腺癌中的表达和功能意义,并可能为基于miRNA的胰腺癌治疗策略和临床检测的设计提供重要信息。

项目成果

期刊论文数量(14)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
p-21 activated kinase 4 promotes proliferation and survival of pancreatic cancer cells through AKT- and ERK-dependent activation of NF-κB pathway.
  • DOI:
    10.18632/oncotarget.2398
  • 发表时间:
    2014-09-30
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Tyagi N;Bhardwaj A;Singh AP;McClellan S;Carter JE;Singh S
  • 通讯作者:
    Singh S
Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells.
  • DOI:
    10.1371/journal.pone.0021573
  • 发表时间:
    2011
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Arora S;Bhardwaj A;Srivastava SK;Singh S;McClellan S;Wang B;Singh AP
  • 通讯作者:
    Singh AP
Modulation of microRNAs by phytochemicals in cancer: underlying mechanisms and translational significance.
  • DOI:
    10.1155/2015/848710
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Srivastava SK;Arora S;Averett C;Singh S;Singh AP
  • 通讯作者:
    Singh AP
MicroRNAs in pancreatic malignancy: progress and promises.
  • DOI:
    10.1016/j.canlet.2014.02.015
  • 发表时间:
    2014-06-01
  • 期刊:
  • 影响因子:
    9.7
  • 作者:
    Srivastava, Sanjeev K.;Arora, Sumit;Singh, Seema;Bhardwaj, Arun;Averett, Courey;Singh, Ajay P.
  • 通讯作者:
    Singh, Ajay P.
Synthesis, characterization, and evaluation of poly (D,L-lactide-co-glycolide)-based nanoformulation of miRNA-150: potential implications for pancreatic cancer therapy.
  • DOI:
    10.2147/ijn.s61949
  • 发表时间:
    2014
  • 期刊:
  • 影响因子:
    8
  • 作者:
    Arora S;Swaminathan SK;Kirtane A;Srivastava SK;Bhardwaj A;Singh S;Panyam J;Singh AP
  • 通讯作者:
    Singh AP
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Ajay Pratap Singh其他文献

Gradually Growing Residual and Self-attention Based Dense Deep Back Projection Network for Large Scale Super-Resolution of Image
用于大规模图像超分辨率的基于残差和自注意力的渐进式密集深背投影网络
  • DOI:
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Manoj Sharma;Avinash Upadhyay;Ajay Pratap Singh;Megh Makwana;Swati Bhugra;Brejesh Lall;S. Chaudhury;Deepak Mishra;Anil K. Saini
  • 通讯作者:
    Anil K. Saini
From modulation of cellular plasticity to potentiation of therapeutic resistance: new and emerging roles of MYB transcription factors in human malignancies
  • DOI:
    10.1007/s10555-023-10153-8
  • 发表时间:
    2023-11-10
  • 期刊:
  • 影响因子:
    8.700
  • 作者:
    Shashi Anand;Kunwar Somesh Vikramdeo;Sarabjeet Kour Sudan;Amod Sharma;Srijan Acharya;Mohammad Aslam Khan;Seema Singh;Ajay Pratap Singh
  • 通讯作者:
    Ajay Pratap Singh
Regional analgesia in neonates undergoing thoracoabdominal surgeries: A pilot study.
接受胸腹手术的新生儿的区域镇痛:一项试点研究。
Harnessing geoinformatics and AHP techniques to assess the groundwater potential zones in Uttar Pradesh, India
  • DOI:
    10.1007/s12518-025-00640-8
  • 发表时间:
    2025-06-26
  • 期刊:
  • 影响因子:
    2.300
  • 作者:
    Sushil Chandra;Ajay Pratap Singh
  • 通讯作者:
    Ajay Pratap Singh
Poor oral intake in a late preterm twin – usual symptom with an unusual diagnosis
晚期早产双胞胎的口腔摄入不良——诊断不寻常的常见症状

Ajay Pratap Singh的其他文献

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{{ truncateString('Ajay Pratap Singh', 18)}}的其他基金

A novel molecular cross-talk driving pancreatic cancer progression
一种驱动胰腺癌进展的新型分子串扰
  • 批准号:
    10093980
  • 财政年份:
    2018
  • 资助金额:
    $ 7.42万
  • 项目类别:
A novel molecular cross-talk driving pancreatic cancer progression
一种驱动胰腺癌进展的新型分子串扰
  • 批准号:
    10335167
  • 财政年份:
    2018
  • 资助金额:
    $ 7.42万
  • 项目类别:
Molecular determinant of racial disparity in prostate cancer
前列腺癌种族差异的分子决定因素
  • 批准号:
    8847693
  • 财政年份:
    2014
  • 资助金额:
    $ 7.42万
  • 项目类别:
Targeting tumor-stromal interaction for pancreatic cancer therapy
针对胰腺癌治疗的肿瘤-基质相互作用
  • 批准号:
    9199071
  • 财政年份:
    2014
  • 资助金额:
    $ 7.42万
  • 项目类别:
Targeting tumor-stromal interaction for pancreatic cancer therapy
针对胰腺癌治疗的肿瘤-基质相互作用
  • 批准号:
    8787996
  • 财政年份:
    2014
  • 资助金额:
    $ 7.42万
  • 项目类别:
Targeting tumor-stromal interaction for pancreatic cancer therapy
针对胰腺癌治疗的肿瘤-基质相互作用
  • 批准号:
    8631528
  • 财政年份:
    2014
  • 资助金额:
    $ 7.42万
  • 项目类别:
Targeting tumor-stromal interaction for pancreatic cancer therapy
针对胰腺癌治疗的肿瘤-基质相互作用
  • 批准号:
    9174192
  • 财政年份:
    2014
  • 资助金额:
    $ 7.42万
  • 项目类别:
Molecular determinant of racial disparity in prostate cancer
前列腺癌种族差异的分子决定因素
  • 批准号:
    8687364
  • 财政年份:
    2014
  • 资助金额:
    $ 7.42万
  • 项目类别:
Molecular determinant of racial disparity in prostate cancer
前列腺癌种族差异的分子决定因素
  • 批准号:
    9045588
  • 财政年份:
    2014
  • 资助金额:
    $ 7.42万
  • 项目类别:
Myb, a key driver of pancreatic cancer progression and metastasis
Myb,胰腺癌进展和转移的关键驱动因素
  • 批准号:
    8285965
  • 财政年份:
    2012
  • 资助金额:
    $ 7.42万
  • 项目类别:

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