文章快速检索     高级检索
   复旦学报(医学版)  2022, Vol. 49 Issue (3): 447-453, 474      DOI: 10.3969/j.issn.1672-8467.2022.03.019
0
Contents            PDF            Abstract             Full text             Fig/Tab
引用本文
张一帆, 周梁. miRNA-148/152家族成员在恶性肿瘤中的生物学功能研究进展[J]. 复旦学报医学版, 2022, 49(3): 447-453.
ZHANG Yi-fan, ZHOU Liang. Progress on biological functions of miRNA-148/152 family members in malignant tumors[J]. Fudan University Journal of Medical Sciences, 2022, 49(3): 447-453.
miRNA-148/152家族成员在恶性肿瘤中的生物学功能研究进展
张一帆 , 周梁     
复旦大学附属眼耳鼻喉科医院耳鼻喉科 上海 200031
收稿日期：2021-02-25；网络首发时间: 2022-03-08 14:14:02
基金项目：国家自然科学基金面上项目（81972529）；上海市科委西医引导项目（19411961300）；上海申康医院发展中心临床研究项目（SHDC2020CR6011）
摘要：microRNA（miRNA）是一类长度约19~25个核苷酸的非编码RNA。在肿瘤中，miRNA能够与靶基因的3'-非翻译区（3'-untranslated region，3'-UTR）完全或不完全配对结合，从而参与调控肿瘤的发生发展等多种生物学过程。microRNA-148/152（miR-148/152）家族成员包括miR-148a、miR-148b和miR-152。与正常组织相比，miR-148/152家族成员在多种恶性肿瘤中低表达，而在少数恶性肿瘤中高表达。近年来，越来越多的研究表明，miR-148/152家族成员在恶性肿瘤的发生发展中发挥极其重要的作用，在多数恶性肿瘤中，miR-148/152家族成员发挥抑癌作用，而在少数恶性肿瘤中，miR-148/152的高表达可能与临床预后不良相关。本文对miR-148/152家族成员在恶性肿瘤中的重要生物学功能和机制进行综述，以期为miRNA治疗靶点提供相关研究信息。
关键词：miR-148/152家族成员    恶性肿瘤    miRNA调控    
Progress on biological functions of miRNA-148/152 family members in malignant tumors
ZHANG Yi-fan , ZHOU Liang     
Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, Shanghai 200031, China
Foundation item: This work was supported by the General Program of National Natural Science Foundation of China (81972529), Western Medicine Guidance Project of Science and Technology Commission of Shanghai Municipality (19411961300) and Clinical Research Project of Shanghai Shenkang Hospital Development Center (SHDC2020CR6011)
Corresponding author: ZHOU Liang, E-mail: zhoulent@126.com.
Abstract: MicroRNA (miRNA) is a type of non-coding RNA with a length of approximately 19-25 nucleotides. In tumors, miRNAs can completely or incompletely bind to the 3'-untranslated region (3'-UTR) of target genes, thereby participating in the regulation of tumor development and other biological processes.The microRNA-148/152 (miR-148/152) family includes microRNA-148a (miR-148a), microRNA-148b (miR-148b) and microRNA-152 (miR-152).The expression of miR-148/152 family in various malignant tumors were different. In recent years, growing studies have shown that the miR-148/152 family members play important roles in the occurrence and development of tumors. In most tumors, the miR-148/152 family members play as tumor suppressor, while in a few tumors, the high expression of miR-148/152 may be related to poor clinical prognosis.We reviewed the role of miR-148/152 family and its important biological functions in malignant tumors, hoping to provide assistance for the treatment in targeting miRNA.
Key words: miR-148/152 family member    malignant tumor    miRNA regulation    

microRNAs（miRNA）是长度约19~25个核苷酸的非编码RNA，对许多生物过程至关重要。microRNA-148/152（miR-148/152）家族的成员，包括miR-148a、miR-148b和miR-152，这一家族在恶性肿瘤的发生发展中扮演了重要的角色。本综述从miRNA的特征和产生、miR-148/152家族成员结构特点、miR-148/152家族成员与靶基因、miR-148/152家族成员的表达与恶性肿瘤的相关性、miR-148/152家族促进肿瘤发生发展的相关机制以及miR-148/152家族在恶性肿瘤免疫逃逸中的作用共六部分进行了系统总结。

miRNA的特征和产生   miRNA长度约19~25个核苷酸，在几乎所有真核细胞中都起着重要的基因表达调节的作用。基因组通过RNA聚合酶Ⅱ转录产生miRNA初始体（pri-miRNA），RNAse Ⅲ内切酶将pri-miRNA切割成miRNA前体（pre-miRNA）[1]。核转运受体Exportin-5将pre-miRNA由细胞核转运至细胞质，随后通过Dicer酶切割pre-miRNA形成成熟的双链miRNA[2]。miRNA是转录后调节因子，通过互补碱基配对与靶基因mRNA的3'-非翻译区（3'-untranslated region，3'-UTR）中的序列结合，从而导致靶基因表达的下调[3]。越来越多的证据表明，miRNA在广泛的生物学过程中起着关键作用，通过表达的上调和下调改变靶基因的表达，从而改变细胞增殖、死亡和能量代谢等多种生物学过程[4]。

miR-148/152家族成员结构特点   miR-148/152家族成员包括miR-148a、miR-148b以及miR-152[5]。miR-148/152家族成员位于人类第7、12和17号染色体。miR-148/152家族成员前体具有茎环结构，该前体通过一系列核内和胞质内酶加工成成熟miR-148/152家族成员。成熟miR-148/152家族成员长度为21~22个核苷酸，相同的种子序列约为6~7个核苷酸（图 1）。种子序列是miRNA与靶mRNA结合的重要区域。通过种子序列与靶mRNA的3'-UTR之间的互补结合，miR-148/152家族成员参与了多种生物学过程。许多恶性肿瘤和正常组织中存在miR-148/152家族成员的差异表达。因此，miR-148/152家族成员对肿瘤的发生和发展可能至关重要。

The respective seed sequences are marked in red. 图 1 miR-148/152家族成员的成熟序列 Fig 1 Mature miRNA sequence of miR-148/152 family members
图选项

miR-148/152家族成员与靶基因   在不同的细胞环境中，相同的miRNA可能通过结合不同的靶基因调节多种途径并引起多种表型。miR-148/152家族成员具有很多不同的靶基因，在多种生物学过程中发挥重要作用。多种生物信息学方法可用于预测miRNA的靶基因。miRanda[6]，Diana-microT-CDS[7]和TargetScan[8]是目前miRNA研究中最常用的3种预测方式。TargetScan使用多种线性回归模型将可分析元素分解为14个特征，然后使用种子匹配（长度和频率）、3′补偿和折叠自由能作为预测特征，是目前科学界使用最广泛的miRNA靶基因预测工具。此外，荧光素酶报告、PCR（polymerase chain reaction）和免疫蛋白印迹（Western blot）等实验方法可用于验证miRNA的靶基因。荧光素酶报告实验可以识别miRNA与其靶向mRNA区域之间的直接相互作用，而qPCR和免疫蛋白印迹可以评估由相互作用引起的转录和翻译抑制。验证miR-148/152的靶基因需满足以下两个标准：靶基因具有带有互补序列的miR-148/152家族成员结合位点，可以直接与miR-148/152家族成员结合；miR-148/152的表达能够抑制靶基因在RNA和蛋白水平上的表达。miR-148/152家族成员的靶基因（表 1）。

表 1 miR-148/152的靶基因及其在恶性肿瘤中的功能 Tab 1 Validated targets of the miR-148/-152 family and its function in malignant tumor
miRNAs Effect Target Tumor types Ref.
miR-148a inhibition of cell migration，invasion，cell proliferation PTEN hepatocellular carcinoma，nasopharyngeal carcinoma [9]
miR-148a，miR-152 tumor proliferation，tumor angiogenesis IGF-IR breast cancer [10]
miR-148b，miR-152 metastasis suppression，cell motility and adhesion CSF1 breast cancer [11]
miR-148a，miR-152 attenuation of drug-resistance ALCAM breast cancer [12]
miR-148a，miR-148b，miR-152 inhibition of immune invasion HLA-G breast cancer，melanoma [13-15]
miR-148a involvement in cell apoptosis c-myc breast cancer [16]
miR-148a involvement in cell apoptosis CTNNB1 breast cancer [16]
miR-148b inhibition of cell migration CTSA breast cancer [17]
miR-148b inhibition of migration ITGA5 breast cancer [17]
miR-148b inhibition of migration MMP15 breast cancer [17]
miR-148b inhibition of migration NRAS breast cancer [17]
miR-148b inhibition of migration PIK3CA breast cancer [17]
miR-148a inhibition of angiogenesis ERBB3 breast cancer，cervical cancer [18]
miR-148a，miR-148b inhibition of migration NRP1 breast cancer，hepatocellular carcinoma [19-20]
miR-148a，miR-148b inhibition of cell proliferation TXNIP breast cancer [21]
miR-148a，miR-148b，miR-152 inhibition of cell migration，invasion，cell proliferation，cell cycle progression HOTAIR breast cancer，gastric cancer [22-23]
miR-152 attenuation of drug-resistance SOS1 glioblastoma [24]
miR-152 inhibition of autophagy ATG14 ovarian cancer [25]
miR-148a，miR-148b，miR-152 inhibition of cell proliferation，migration，and invasion ROCK1 gastric cancer，hepatocellular carcinoma [17]
miR-148a，miR-148b tumor proliferation CCKBR gastric cancer [26]
miR-148a，miR-148b，miR-152 inhibition of cell proliferation and migration DNMT1 gastric cancer，hepatocellular carcinoma，bladder cancer [27-29]
miR-148a induction of apoptosis Bcl-2 gastric cancer，colorectal cancer [30]
miR-148a inhibition of cell proliferation P27 gastric cancer [31]
miR-148a inhibition of migration and invasion SMAD2 gastric cancer [32]
miR-148a tumor invasion MMP7 gastric cancer [33]
miR-152 inhibition of cell proliferation and invasion TXNIP melanoma [34]
miR-152 tumor suppressor PIK3R3 colorectal cancer [35]
miR-148a inhibition of migration WNT10B endometrial cancer [36]
miR-148a suppression of tumor angiogenesis SKP1 glioma [32]
miR-152 inhibition of cell proliferation MIG6 glioma [37]
miR-148a inhibition of cell proliferation，migration，and invasion HPIP hepatocellular carcinoma [38]
miR-152 inhibition of tumor proliferation KIT hepatocellular carcinoma [39]
miR-148a inhibition of migration and invasion MET hepatocellular carcinoma [40]
miR-152 involvement in the formation and progression of gstp-positive preneoplastic lesions TFRC hepatocellular carcinoma [41]
miR-148a inhibition of cell proliferation and migration USP4 hepatocellular carcinoma [42]
miR-148a，miR-148b，miR-152 inhibition of migration and invasion WNT1 hepatocellular carcinoma [43]
miR-148a tumor suppressor RUNX3 laryngeal squamous cell carcinoma，glioma [44-45]
miR-148a promotion tumor proliferation CAND1 prostate cancer [46]
miR-148a attenuation of drug-resistance MSK1 prostate cancer [47]
miR-152 promotion of tumor migration and invasion TGFɑ prostate cancer [48]
miR-148a，miR-148b，miR-152 promotion of tumor proliferation KLF4 prostate cancer [49-50]
miR-152 inhibition of cell proliferation and migration TNS1 non-small cell lung cancer [51]
miR-152 inhibition of cell proliferation ADAM17 non-small cell lung cancer [52]
miR-148b inhibition of cell proliferation and migration CEA non-small cell lung cancer [53]
miR-152 promotion of tumor proliferation and invasion FGF2 non-small cell lung cancer [54]
miR-148a，miR-148b attenuation of drug-resistance EGFR malignant pleural mesothelioma [55]
miR-152 inhibition of tumor proliferation MKK7 ovarian adenocarcinoma [56]
表选项

miR-148/152家族成员的表达与恶性肿瘤的相关性   miR-148/152家族成员在许多恶性肿瘤中表达上调。据报道，包括miR-148a在内的6种miRNA在多发性骨髓瘤（multiple myeloma，MM）血浆中显著上调，高水平的miR-148a与更短的无复发生存时间相关[57]。同样在血浆中，Cuk等[58]注意到miR-148b在乳腺癌患者中明显上调。此外，Gokhale等[59]发现miR-148a在髓母细胞瘤中过表达，并可能与WNT信号通路相关。另外，miR-148a在与肝细胞癌（hepatocellular，HCC）相关的乙型肝炎细胞中被上调[60]。因此，在这些肿瘤中，miR-148a和miR-148b可能是重要的生物标志物，并具有早期诊断的潜在价值。

在多种恶性肿瘤类型中发现miR-148/152家族成员的表达都有下调，表明它们可能具有肿瘤抑制的作用。在肝细胞癌中，相对于肝细胞系L02，miR-148b在肝癌细胞系HepG2、MHCC97L和MHCC97H中表达下调[60]。miR-148a和miR-152在胃肠道肿瘤组织及其细胞系中的表达被下调，并通过靶向胆囊收缩素-2受体（cholecystokinin B receptor，CCK2R）抑制细胞生长[26]。在卵巢癌组织及其细胞系中，miR-152表达降低，但miR-148a仅在卵巢癌细胞系中表达降低[61]。

miR-148/152家族促进肿瘤发生发展的相关机制   目前在许多肿瘤中都发现了miR-148/152家族成员基因的甲基化。此前有研究发现，在胃癌中，DNMT1（DNA methyltransferase 1）的过表达能够促进miR-148a基因启动子的超甲基化从而抑制其表达，而沉默miR-148a会降低其对DNMT1的抑制作用，这可能会导致DNMT1的过表达，从而促进DNA超甲基化[62]。Lujambio等[63]发现使用DNA脱甲基剂后，与正常组织相比，miR-148a、miR-34b/c和miR-9在癌细胞中出现了特定的高甲基化相关沉默；最重要的是，他们发现与DNA甲基化相关的抑癌miRNA沉默可能有助于人类癌症的转移。Stumpel等[64]鉴定出11种miRNA，包括miR-152，它们由于CpG甲基化而在t（4；11）阳性婴儿急性淋巴细胞白血病中下调。进一步的研究表明，髓样/淋巴样白血病（myeloid-lymphoid leukemia，MLL）中，DNMT1是miR-152的潜在靶基因，miR-152 CpG岛的高度甲基化与不良的临床预后密切相关。

近年来多项研究表明miR-148/152家族成员通过靶向多条通路从而产生对肿瘤的抑制作用。Feng等[49]发现前列腺癌中miR-148-3p和miR-152-3p可通过抑制KLF4（Kruppel like factor 4）发挥抗肿瘤作用。除前列腺癌外，结直肠癌等多种肿瘤中都发现miR-148/152家族成员可靶向KLF4并抑制肿瘤的生长[50]。在乳腺癌中，miR-152的过表达通过靶向IGF-1R（insulin-like growth factor 1 receptor）和IRS1（insulin receptor substrate 1）并抑制其下游AKT和MAPK信号通路来显著抑制细胞增殖、集落形成和肿瘤血管生成[10]。非小细胞肺癌中，miR-152/TNS1轴通过Akt/mTOR/RhoA通路抑制肿瘤的增殖和迁移[51]。

DNMT1是一种DNA甲基转移酶，在疾病的发生发展中发挥重要的作用。研究表明，DNMT1在多种肿瘤中差异表达[65]，并能被miR-148/152家族成员调节其表达，包括肝细胞癌[27]、急性淋巴细胞白血病[28]、子宫内膜癌[29]等。在乳腺癌中，多项研究表明miR-148a/152-DNMT1调节回路在肿瘤的发生发展中发挥极其重要的作用[10]。

PTEN（phosphatase and tensin homolog）是一种磷酸酶，可催化脂质第二信使PtdIns（3，4，5）P3转化为磷脂酰肌醇（4，5）-双磷酸[PtdIns（4，5）P2][66]。PTEN突变在多种肿瘤中频繁发生，例如子宫内膜癌[67]、多形胶质母细胞瘤[68]、皮肤[69]和前列腺癌[70]。据报道，PTEN作为靶基因受多种基因调控。在miR-148/152家族成员中，miR-148a和miR-152已被实验证实可调控PTEN的表达[9]，但相关研究仍较少，需要进一步探究。此外，一项关于膀胱癌的研究表明，miR-152-3p通过抑制DNMT1来调节PTEN启动子中DNA甲基化的状态从而调控PTEN的表达[71]。

CAND1（cullin associated and neddylation dissociated 1）等基因也被证明是miR-148/152家族成员的靶基因，并调控恶性肿瘤的发生与发展。Murata等[46]发现miR-148a通过与CAND1 mRNA的3'-UTR结合而降低了CAND1的表达，并促进了人类前列腺癌的生长。此外，Bcl-2[30]，p27[31]和CSF-1（colony stimulating factor 1）[11]也被证明是miR-148/152家族成员的靶基因。

miR-148/152家族成员与恶性肿瘤对药物的敏感性也密切相关。在胶质母细胞瘤细胞（T98G和U87）中，miR-152-3p通过靶向SOS1（SOS Ras/Rac guanine nucleotide exchange factor 1）增强了对顺铂的敏感性[24]，在卵巢癌顺铂耐药系细胞中，miR-152的表达显著下调。进一步研究发现，miR-152可以通过调控ATG14（autophagy related 14）减少顺铂诱导的自噬，增强顺铂诱导的细胞凋亡和抑制细胞增殖[25]。在乳腺癌中，miR-148a和miR-152通过调控ALCAM（activated leukocyte cell adhesion molecule）的表达，降低ER+乳腺癌的他莫昔芬耐药性[12]。

miR-148/152家族在恶性肿瘤免疫逃逸中的作用   人白细胞抗原G（major histocompatibility complex，class I，G，HLA-G）是一类在孕妇中对胎儿提供免疫耐受保护的重要蛋白。研究发现，HLA-G也具有免疫抑制的作用，在肿瘤的发生发展中作为免疫检查点发挥重要的功能。在多种不同起源的人类肿瘤中，HLA-G经常表达，从而抑制T细胞和自然杀伤（nature killer，NK）细胞的细胞毒活性。HLA-G能在免疫细胞（NK、T、B、单核细胞/树突状细胞）上牢固结合其抑制性受体，抑制这些免疫细胞的功能，诱导免疫抑制。当肿瘤表达HLA-G时，可保护其免受抗肿瘤免疫的杀伤[13]。最近的研究表明，miR-148/152对HLA-G的转录后基因调控很强。Fu等[14]的研究表明，在非小细胞肺癌中，miR-152能够靶向HLA-G，调控其表达并影响肿瘤对NK细胞的免疫逃避。研究表明，miR-148在肾细胞癌中与HLA-G mRNA直接结合并调控其表达。HLA-G表达的肾细胞癌细胞系（NIH/3TS）中，miR-152的过表达能大幅下调HLA-G的表达并增进其对NK或LAK（lymphokine activated killer）细胞介导的细胞毒性[15]。

结语   目前已发现miR-148/152家族成员在多种恶性肿瘤中差异表达并发挥不同的作用。无论是在组织中上调还是下调，miR-148/152家族成员都参与靶基因的调节并调控多种信号通路，影响细胞的增殖、分化和凋亡。同时，miR-148/152家族成员在增强肿瘤对药物敏感性以及免疫逃逸中都发挥了重要作用。miR-148/152受到其CpG岛甲基化的调节，并可能存在miR-148a/152-DNMT1调节环路。尽管近年来对于miR-148/152家族的研究取得了很大进展，然而，关于其在不同肿瘤和组织中的功能仍不清楚，尤其是miR-148/152家族在肿瘤的免疫逃逸等多种生物学过程中的功能和分子机制仍亟待更多的研究探讨。

作者贡献声明  张一帆  文献查阅，绘制图表，论文撰写和修订。周梁  获取资助，论文指导和修订。

利益冲突声明  所有作者均声明不存在利益冲突。

参考文献
[1]
LEE Y, KIM M, HAN J, et al. MicroRNA genes are transcribed by RNA polymerase Ⅱ[J]. EMBO J, 2004, 23(20): 4051-4060. [DOI]
[2]
YI R, QIN Y, MACARA IG, et al. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs[J]. Genes Dev, 2004, 17(24): 3011-3016.
[3]
BARTEL DP. MicroRNAs: genomics, biogenesis, mechanism, and function[J]. Cell, 2004, 116(2): 281-297. [DOI]
[4]
AMBROS V, LEE RC, LAVANWAY A, et al. MicroRNAs and other tiny endogenous RNAs in C. elegans[J]. Curr Biol, 2003, 13(10): 807-818. [DOI]
[5]
CHEN Y, SONG Y, WANG Z, et al. Altered expression of MiR-148a and MiR-152 in gastrointestinal cancers and its clinical significance[J]. J Gastrointest Sur, 2010, 14(7): 1170-1179. [DOI]
[6]
WESSELS HH, LEBEDEVA S, HIRSEKORN A, et al. Global identification of functional microRNA-mRNA interactions in Drosophila[J]. Nat Commun, 2019, 10(1): 1626. [DOI]
[7]
KIRIAKIDOU M. A combined computational-experimental approach predicts human microRNA targets[J]. Genes Dev, 2004, 18(10): 1165-1178. [DOI]
[8]
LEWIS BP, SHIH IH, JONES-RHOADES MW, et al. Prediction of mammalian microRNA targets[J]. Cell, 2003, 115(7): 787-798. [DOI]
[9]
HUANG S, LI X, ZHU H. MicroRNA-152 targets phosphatase and tensin homolog to inhibit apoptosis and promote cell migration of nasopharyngeal carcinoma Cells[J]. Med Sci Monit, 2016, 22: 4330-4337. [DOI]
[10]
XU Q, JIANG Y, YIN Y, et al. A regulatory circuit of miR-148a/152 and DNMT1 in modulating cell transformation and tumor angiogenesis through IGF-IR and IRS1[J]. J Mol Cell Biol, 2013, 5(1): 3-13. [DOI]
[11]
WOO HH, CSABA FL, GRECO S, et al. Regulation of colony stimulating factor-1 expression and ovarian cancer cell behavior in vitro by miR-128 and miR-152[J]. Mol Cancer, 2012, 11(1): 58. [DOI]
[12]
CHEN MJ, CHENG YM, CHEN CC, et al. MiR-148a and miR-152 reduce tamoxifen resistance in ER+ breast cancer via downregulating ALCAM[J]. Biochem Biophys Res Commun, 2017, 483(2): 840-846. [DOI]
[13]
KRIJGSMAN D, ROELANDS J, HENDRICKX W, et al. HLA-G: A new immune checkpoint in cancer[J]. Int J Mol Sci, 2020, 21(12): 4528. [DOI]
[14]
FU J, MAO J, WANG C. The microRNA-152/human leukocyte antigen-G axis affects proliferation and immune escape of non-small cell lung cancer cells[J]. J Int Med Res, 2020, 48(11): 30006052097075. [DOI]
[15]
JASINSKI-BERGNER S, STOEHR C, BUKUR J, et al. Clinical relevance of miR-mediated HLA-G regulation and the associated immune cell infiltration in renal cell carcinoma[J]. Oncoimmunology, 2015, 4(6): e1008805. [DOI]
[16]
LI F, LIU W, SONG Z, et al. miR-148a overexpression inhibits cell proliferation and induces cell apoptosis by suppressing the Wnt/β-catenin signal pathway in breast cancer MCF-7 cells[J]. Int J Clin Exp Pathol, 2016, 9(3): 3349-3356.
[17]
CIMINO D, DE PITTA C, ORSO F, et al. miR148b is a major coordinator of breast cancer progression in a relapse-associated microRNA signature by targeting ITGA5, ROCK1, PIK3CA, NRAS, and CSF1[J]. FASEB J, 2013, 27(3): 1223-1235. [DOI]
[18]
YU J, LI Q, XU Q, et al. MiR-148a inhibits angiogenesis by targeting ERBB3[J]. J Biomed Res, 2011, 25(3): 170-177. [DOI]
[19]
XU X, ZHANG Y, JASPER J, et al. MiR-148a functions to suppress metastasis and serves as a prognostic indicator in triple-negative breast cancer[J]. Oncotarget, 2016, 7(15): 20381-20394. [DOI]
[20]
LIU Q, XU Y, WEI S, et al. miRNA-148b suppresses hepatic cancer stem cell by targeting neuropilin-1[J]. Biosci Rep, 2015, 35(4): e00229.
[21]
OKUMURA S, YU H, KOMATSU Y. Stable duplex-linked antisense targeting miR-148a inhibits breast cancer cell proliferation[J]. Sci Rep, 2021, 11(1): 11467. [DOI]
[22]
SONG B, GUAN Z, LIU F, et al. Long non-coding RNA HOTAIR promotes HLA-G expression via inhibiting miR-152 in gastric cancer cells[J]. Biochem Biophys Res Commun, 2015, 464(3): 807-813. [DOI]
[23]
WANG G, LI Z, TIAN N, et al. miR-148b-3p inhibits malignant biological behaviors of human glioma cells induced by high HOTAIR expression[J]. Oncol Lett, 2016, 12(2): 879-886. [DOI]
[24]
WANG M, WU Q, FANG M, et al. miR-152-3p sensitizes glioblastoma cells towards cisplatin via regulation of SOS1[J]. Onco Targets Ther, 2019, 12: 9513-9525. [DOI]
[25]
HE J, YU JJ, XU Q, et al. Downregulation of ATG14 by EGR1-MIR152 sensitizes ovarian cancer cells to cisplatin-induced apoptosis by inhibiting cyto-protective autophagy[J]. Autophagy, 2015, 11(2): 373-384. [DOI]
[26]
SONG Y, XU Y, WANG Z, et al. MicroRNA-148b suppresses cell growth by targeting cholecystokinin-2 receptor in colorectal cancer[J]. Int J Cancer, 2012, 131(5): 1042-1051. [DOI]
[27]
HUANG J, WANG Y, GUO Y, et al. Down-regulated microRNA-152 induces aberrant DNA methylation in hepatitis B virus-related hepatocellular carcinoma by targeting DNA methyltransferase 1[J]. Hepatology, 2010, 52(1): 60-70. [DOI]
[28]
STUMPEL DJPM, SCHOTTE D, LANGE-TURENHOUT E AM, et al. Hypermethylation of specific microRNA genes in MLL-rearranged infant acute lymphoblastic leukemia: major matters at a micro scale[J]. Leukemia, 2011, 25(3): 429. [DOI]
[29]
TSURUTA T, KOZAKI K I, UESUGI A, et al. miR-152 is a tumor suppressor microRNA that is silenced by DNA hypermethylation in endometrial cancer[J]. Cancer Res, 2011, 71(20): 6450-6462. [DOI]
[30]
ZHANG H, LI Y, HUANG Q, et al. MiR-148a promotes apoptosis by targeting Bcl-2 in colorectal cancer[J]. Cell Death Differ, 2011, 18(11): 1702-1710. [DOI]
[31]
GUO SL, ZHENG P, XUE Y, et al. miR-148a promoted cell proliferation by targeting p27 in gastric cancer cells[J]. Int J Biol Sci, 2011, 7(5): 567-574. [DOI]
[32]
WANG H, PAN JQ, LUO L, et al. NF-κB induces miR-148a to sustain TGF-β/Smad signaling activation in glioblastoma[J]. Mol Cancer, 2015, 14: 2. [DOI]
[33]
SAKAMOTO N, NAITO Y, OUE N, et al. MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis[J]. Cancer Sci, 2014, 105(2): 236-243. [DOI]
[34]
LI K, TANG M, TONG S, et al. BRAFi induced demethylation of miR-152-5p regulates phenotype switching by targeting TXNIP in cutaneous melanoma[J]. Apoptosis, 2020, 25(7653): 179-191.
[35]
LI B, XIE Z, LI B. miR-152 functions as a tumor suppressor in colorectal cancer by targeting PIK3R3[J]. Tumour Biol, 2016, 37(8): 1-10.
[36]
APRELIKOVA O, PALLA J, HIBLER B, et al. Silencing of miR-148a in cancer-associated fibroblasts results in WNT10B-mediated stimulation of tumor cell motility[J]. Oncogene, 2013, 32(27): 3246-3253. [DOI]
[37]
MA J, YAO Y, WANG P, et al. MiR-152 functions as a tumor suppressor in glioblastoma stem cells by targeting Kruppel-like factor 4[J]. Cancer Lett, 2014, 355(1): 85-95. [DOI]
[38]
XU X, FAN Z, KANG L, et al. Hepatitis B virus X protein represses miRNA-148a to enhance tumorigenesis[J]. J Clin Invest, 2013, 123(2): 630-645.
[39]
HUANG H, HU M, LI P, et al. Mir-152 inhibits cell proliferation and colony formation of CD133+ liver cancer stem cells by targeting KIT[J]. Tumour Biol, 2015, 36(2): 921-928. [DOI]
[40]
ZHANG JP, ZENG C, XU L, et al. MicroRNA-148a suppresses the epithelial-mesenchymal transition and metastasis of hepatoma cells by targeting Met/Snail signaling[J]. Oncogene, 2013, 33(31): 4069-4076.
[41]
KINDRAT I, TRYNDYAK V, DE CONTI A, et al. MicroRNA-152-mediated dysregulation of hepatic transferrin receptor 1 in liver carcinogenesis[J]. Oncotarget, 2016, 7(2): 1276-1287. [DOI]
[42]
HEO MJ, KIM YM, KOO JH, et al. microRNA-148a dysregulation discriminates poor prognosis of hepatocellular carcinoma in association with USP4 overexpression[J]. Oncotarget, 2014, 5(9): 2792-2806. [DOI]
[43]
ZHANG JG, SHI Y, HONG DF, et al. MiR-148b suppresses cell proliferation and invasion in hepatocellular carcinoma by targeting WNT1/β-catenin pathway[J]. Rep, 2015, 5: 8087.
[44]
JILI S, ERYONG L, LIJUAN L, et al. RUNX3 inhibits laryngeal squamous cell carcinoma malignancy under the regulation of miR-148a-3p/DNMT1 axis[J]. Cell Biochem Funct, 2016, 34(8): 597-605. [DOI]
[45]
LI Y, CHEN F, CHU J, et al. miR-148-3p inhibits growth of glioblastoma targeting DNA methyltransferase-1 (DNMT1)[J]. Oncol Res, 2019, 27(8): 911-921. [DOI]
[46]
MURATA T, TAKAYAMA K, KATAYAMA S, et al. miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression[J]. Prostate Cancer Prostatic Dis, 2010, 13(4): 356-361. [DOI]
[47]
FUJITA Y, KOJIMA K, OHHASHI R, et al. MiR-148a attenuates paclitaxel resistance of hormone-refractory, drug-resistant prostate cancer PC3 cells by regulating MSK1 expression[J]. J Biol Chem, 2010, 285(25): 19076-19084. [DOI]
[48]
ZHU C, LI J, DING Q, et al. MiR-152 controls migration and invasive potential by targeting TGFα in prostate cancer cell lines[J]. Prostate, 2013, 73(10): 1082-1089. [DOI]
[49]
FENG F, LIU H, CHEN A, et al. miR-148-3p and miR-152-3p synergistically regulate prostate cancer progression via repressing KLF4[J]. J Cell Biochem, 2019, 120(10): 17228-17239. [DOI]
[50]
ZHU X, SHEN Z, MAN D, et al. miR-152-3p Affects the Progression of Colon Cancer via the KLF4/IFITM3 Axis[J]. Comput Math Methods Med, 2020, 2020: 8209504.
[51]
DUAN J, WANG L, SHANG L, et al. miR-152/TNS1 axis promotes non-small cell lung cancer progression through Akt/mTOR/RhoA pathway[J]. Biosci Rep, 2020, 41(1): BSR20201539.
[52]
SU Y, WANG Y, ZHOU H, et al. MicroRNA-152 targets ADAM17 to suppress NSCLC progression[J]. FEBS Lett, 2016, 588(10): 1983-1988.
[53]
LIU GL, LIU X, LV XB, et al. miR-148b functions as a tumor suppressor in non-small cell lung cancer by targeting carcinoembryonic antigen (CEA)[J]. Int J Clin Exp Med, 2014, 7(8): 1990-1999.
[54]
CHENG Z, MA R, TAN W, et al. MiR-152 suppresses the proliferation and invasion of NSCLC cells by inhibiting FGF2[J]. Exp Mol Med, 2014, 46(9): e112. [DOI]
[55]
YUEN ML, ZHUANG L, RATH EM, et al. The role of E-cadherin and microRNA on FAK inhibitor response in malignant pleural mesothelioma (MPM)[J]. Int J Mol Sci, 2021, 22(19): 10225. [DOI]
[56]
ZHANG G, ZHENG D, CHEN X, et al. miR-152-mediated MKK7 downregulation is attenuated by MYCNOS in ovarian adenocarcinoma[J]. Oncol Lett, 2021, 22(6): 841. [DOI]
[57]
HUANG JJ, YU J, LI JY, et al. Circulating microRNA expression is associated with genetic subtype and survival of multiple myeloma[J]. Med Oncol, 2012, 29(4): 2402-2408. [DOI]
[58]
CUK K, ZUCKNICK M, HEIL J, et al. Circulating microRNAs in plasma as early detection markers for breast cancer[J]. Int J Cancer, 2013, 132(7): 1602-1612. [DOI]
[59]
GOKHALE A, KUNDER R, GOEL A, et al. Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway[J]. J Cancer Res Ther, 2010, 6(4): 521-529. [DOI]
[60]
赵越, 贾户亮, 周海军, 等. 肝癌转移相关的微小RNAs在不同转移潜能肝癌细胞系的定量研究[J]. 中华肝脏病杂志, 2009, 17(7): 526-530. [DOI]
[61]
ZHOU X, ZHAO F, WANG ZN, et al. Altered expression of miR-152 and miR-148a in ovarian cancer is related to cell proliferation[J]. Oncol Rep, 2012, 27(2): 447-454.
[62]
ZHU A, XIA J, ZUO J, et al. MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in gastric cancer[J]. Med Oncol, 2012, 29(4): 2701-2709. [DOI]
[63]
LUJAMBIO A, CALIN GA, VILLANUEVA A, et al. A microRNA DNA methylation signature for human cancer metastasis[J]. Proc Natl Acad Sci U S A, 2008, 105(36): 13556-13561. [DOI]
[64]
STUMPEL DJPM, SCHOTTE D, LANGE-TURENHOUT EAM, et al. Hypermethylation of specific microRNA genes in MLL-rearranged infant acute lymphoblastic leukemia: major matters at a micro scale[J]. Leukemia, 2011, 25(3): 429. [DOI]
[65]
ROBERTSON KD, UZVOLGYI E, LIANG G, et al. The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors[J]. Nucleic Acids Res, 1999, 27(11): 2291-2298. [DOI]
[66]
MAEHAMA T, DIXON JE. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3, 4, 5-trisphosphate[J]. J Biol Chem, 1998, 273(22): 13375-13378. [DOI]
[67]
RISINGER JI, HAYES A K, BERCHUCK A, et al. PTEN/MMAC1 mutations in endometrial cancers[J]. Cancer Res, 1997, 57(21): 4736.
[68]
WANG SI, PUC J, LI J, et al. Somatic mutations of PTEN in glioblastoma multiforme[J]. Cancer Res, 1997, 57(19): 4183-4186.
[69]
KUBO, Y. Lack of somatic mutation in the PTEN gene in squamous cell carcinomas of human skin[J]. J Dermatol Sci, 1999, 19(3): 199-201. [DOI]
[70]
CAIRNS P, OKAMI K, HALACHMI S, et al. Frequent inactivation of PTEN/MMAC1 in primary prostate cancer[J]. Cancer Res, 1997, 57(22): 4997-5000.
[71]
LIU P, WU L, CHAND H, et al. Silencing of miR-152 contributes to DNMT1-mediated CpG methylation of the PTEN promoter in bladder cancer[J]. Life Sci, 2020, 261: 118311. [DOI]

文章信息

张一帆, 周梁
ZHANG Yi-fan, ZHOU Liang
miRNA-148/152家族成员在恶性肿瘤中的生物学功能研究进展
Progress on biological functions of miRNA-148/152 family members in malignant tumors
复旦学报医学版, 2022, 49(3): 447-453.
Fudan University Journal of Medical Sciences, 2022, 49(3): 447-453.
Corresponding author
ZHOU Liang, E-mail: zhoulent@126.com.
基金项目
国家自然科学基金面上项目（81972529）；上海市科委西医引导项目（19411961300）；上海申康医院发展中心临床研究项目（SHDC2020CR6011）
Foundation item
This work was supported by the General Program of National Natural Science Foundation of China (81972529), Western Medicine Guidance Project of Science and Technology Commission of Shanghai Municipality (19411961300) and Clinical Research Project of Shanghai Shenkang Hospital Development Center (SHDC2020CR6011)

工作空间