Locked nucleic acid anti-miR-21 inhibits cell growth and invasive behaviors of a colorectal adenocarcinoma cell line: LNA-anti-miR as a novel approach
Locked nucleic acid anti-miR-21 inhibits cell growth and invasive behaviors of a colorectal adenocarcinoma cell line: LNA-anti-miR as a novel approach
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DOI：
10.1038/cgt.2016.25
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发表时间：
2016-08-01
影响因子：
6.4
通讯作者：
Salehi, R.
中科院分区：
文献类型：
--
作者：
Nedaeinia, R.;Sharifi, M.;Salehi, R.
结直肠癌（CRC）是癌症相关死亡的第三大原因，预后极差。已证明微小RNA（miRNA）的失调与许多恶性肿瘤的发病机制和进展有关。最近的数据表明，microRNA-21（miR-21）在不同类型的癌症中显著升高，尤其是结肠腺癌。在这种背景下，锁核酸（LNA）修饰的寡核苷酸最近被认为是一种新的方法。面向. miRNAs作为反义基因沉默。本研究的目的是探讨LNA-抗miR-21在结肠腺癌LS 174 T细胞系中的功能作用。用LNA-抗-miR-21转染LS 174 T细胞24、48和72 h。进行定量实时逆转录酶-PCR（qRT-PCR）以：通过LNA-抗-miR-21评估miR-21表达。MTT法检测细胞活力，Annexin V/propidium iodide染色法检测细胞凋亡。transwell法检测治疗前后细胞的侵袭行为。LNA-抗-miR-21成功转染人LS 174 T细胞并抑制内源性miR-21。LNA-抗-miR-21抑制细胞生长，随后诱导细胞凋亡。与未处理的细胞和乱序LNA转染的细胞相比，LNA-抗-miR-21（50 pmol/μ l）在24小时后降低了LS 174T细胞的侵袭行为。然而，这种作用在72 h后更明显。我们的研究结果表明LNA-抗-miR-21在结肠腺癌中靶向miR-21表达的治疗潜力。需要进一步研究这种新型抑制剂在结直肠癌中的分子机制，以确定其治疗高miR-21表达的CRC患者的潜在价值。
Colorectal cancer (CRC) is the third leading cause of cancer-related death and has an extremely poor prognosis. Dysregulation of microRNAs (miRNAs) has been shown to be involved in the pathogenesis and progression of many malignancies. Recent data suggest that microRNA-21 (miR-21) is significantly elevated in different types of cancer, especially colon adenocarcinoma. Against this background, locked nucleic acid (LNA)-modified oligonucleotides have recently been suggested as a novel approach for. targeting. miRNAs as antisense-based gene silencing. The aim of the current study was to explore the functional role of LNA-anti-miR-21 in-a colon adenocarcinoma LS174T cell line. LS174T cells were transfected with LNA-anti-miR-21 for 24, 48 and 72 h. Quantitative real-time reverse transctiptase-PCR (qRT-PCR) was performed to:assess miR-21 expression by LNA-anti-miR-21. The viability of the cells was evaluated by MTT (3[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay and Annexin V/propidium iodide staining assay was used to detect apoptosis. Moreover, invasive behavior of the cells was evaluated before and after therapy by transwell assay. LNA-anti-miR-21 was successfully transfected: in human LS174T cells and suppressed the endogenous miR-21. LNA-anti-miR-21 inhibited the cells' growth followed by induction of apoptosis. LNA-anti-miR-21 (50 pmol/mu l) reduced the invasive behaviors of LS174T cells after 24 h, compared with untreated cells and scrambled LNA-transfected cells. However, this effect was more pronounced after 72 h. Our findings suggest the therapeutic potential of LNA-anti-miR-21 in a colon adenocarcinoma for targeting miR-21 expression. Further studies are warranted to investigate the molecular mechanisms underlying this novel inhibitor in colorectal cancer to establish its potential value for treatment of CRC patients with high miR-21 expression.