Antisense oligonucleotide mediated knockdown of HOXC13 affects cell growth and induces apoptosis in tumor cells and over expression of HOXC13 induces 3D-colony formation.

Antisense oligonucleotide mediated knockdown of HOXC13 affects cell growth and induces apoptosis in tumor cells and over expression of HOXC13 induces 3D-colony formation.
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DOI:
10.1039/c2ra22006g
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发表时间:
2013-01-01
期刊:
影响因子:
3.9
通讯作者:
Mandal SS
Mandal SS
中科院分区:
化学3区
文献类型:
--
作者:
Kasiri S;Ansari KI;Hussain I;Bhan A;Mandal SS

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HOXC13是一个同源盒,包含在头发发育和复制起源中起关键作用的基因。在此,我们研究了HOXC13的生化功能,并探讨了其在肿瘤细胞活力中的潜在作用。我们设计了一种基于硫代酸的反义寡核苷酸,可以在培养细胞中特异性地敲除HOXC13。细胞活力和细胞毒性实验表明,HOXC13对细胞生长和活力至关重要。反义介导的HOXC13基因敲低影响肿瘤细胞活力,诱导肿瘤细胞凋亡。HOXC13调节细胞周期蛋白的表达,反义介导的HOXC13敲低导致结肠癌细胞周期阻滞和细胞凋亡。最后,在软琼脂实验中,过表达HOXC13导致3d集落形成,表明其在细胞增殖和肿瘤发生中的潜在作用。
HOXC13 is a homeobox containing gene that plays crucial roles in hair development and origin of replication. Herein, we investigated the biochemical functions of HOXC13 and explored its potential roles in tumor cell viability. We have designed a phosphorothioate based antisense-oligonucleotide that specifically knockdown HOXC13 in cultured cells. Cell viability and cytotoxicity assays demonstrated that HOXC13 is essential for cell growth and viability. Antisense-mediated knockdown of HOXC13 affected the cell viability and induced apoptosis in cultured tumor cells. HOXC13 regulates the expression of cyclins and antisense-mediated knockdown of HOXC13 resulted in cell cycle arrest and apoptosis in colon cancer cells. Finally over expression of HOXC13 resulted in 3D-colony formation in soft-agar assay indicating its potential roles in cell proliferation and tumorigenesis.