The long noncoding RNA HOXA transcript at the distal tip promotes colorectal cancer growth partially via silencing of p21 expression
The long noncoding RNA HOXA transcript at the distal tip promotes colorectal cancer growth partially via silencing of p21 expression
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DOI：
10.1007/s13277-015-4617-2
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发表时间：
2016-06-01
期刊：
影响因子：
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通讯作者：
Wang, Keming
中科院分区：
文献类型：
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作者：
Lian, Yifan;Ding, Jie;Wang, Keming
越来越多的证据强烈表明，长链非编码rna （lncRNAs）的失调与人类癌变有关。lncRNA远端HOXA转录本（HOTTIP）参与了几种癌症的发展。然而，HOTTIP在结直肠癌（CRC）中的生物学作用尚未得到讨论。在这里，我们报道HOTTIP在结直肠癌的发病机制中作为一个功能性癌基因。本研究采用定量聚合酶链反应（qPCR）检测HOTTIP在48对结直肠癌样本中的表达。我们发现HOTTIP的过表达与肿瘤的晚期病理分期和较大的肿瘤大小有关。功能分析表明，小干扰RNA （small interfering RNA, siRNA）或小发夹RNA （small hairpin RNA, shRNA）敲低HOTTIP的表达可抑制细胞增殖，诱导细胞凋亡。更重要的是，我们观察到HOTTIP敲除诱导DLD-1细胞和SW480细胞中G0/G1期细胞数量显著增加，S期细胞数量显著减少。体内实验也表明，敲低HOTTIP可抑制肿瘤生长。Western blot和免疫组织化学分析表明，HOTTIP可能通过沉默p21的表达部分促进结直肠癌细胞的生长。总的来说，我们的结果表明HOTTIP参与了CRC的进展，并可能为HOTTIP作为治疗该疾病的靶点提供证据。
Accumulating evidence strongly suggests that dysregulation of long noncoding RNAs (lncRNAs) is associated with human carcinogenesis. The lncRNA HOXA transcript at the distal tip (HOTTIP) is involved in the development of several cancers. However, the biological role of HOTTIP in colorectal cancer (CRC) has not yet been discussed. Here, we report that HOTTIP acts as a functional oncogene in the pathogenesis of CRC. In this study, quantitative polymerase chain reaction (qPCR) was performed to detect the expression of HOTTIP in 48 pairs of colorectal cancer samples. We found that overexpression of HOTTIP is correlated with an advanced pathological stage and a larger tumor size. Moreover, functional analyses revealed that the knockdown of HOTTIP expression by small interfering RNA (siRNA) or small hairpin RNA (shRNA) could inhibit cell proliferation and induce cell apoptosis. More importantly, we observed that HOTTIP knockdown induced a marked increase in the number of cells in the G0/G1 phase and a reduction in the number of cells in the S phase in both DLD-1 cells and SW480 cells. An in vivo experiment also revealed that the knockdown of HOTTIP inhibited tumor growth. Western blot and immunohistochemistry analyses indicated that HOTTIP potentially contributed to CRC cell growth partially through the silencing of p21 expression. Collectively, our results suggest that HOTTIP is involved in the progression of CRC and may provide evidence for HOTTIP being a target for therapy of this disease.