长链非编码 RNA LINC01234 通过竞争性结合 miR-642a-5p 促进结肠癌丝氨酸羟甲基转移酶 2 的表达和增殖。

Long noncoding RNA LINC01234 promotes serine hydroxymethyltransferase 2 expression and proliferation by competitively binding miR-642a-5p in colon cancer.

机构信息

Department of Gastrointestinal surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan, 410013, China.

College of Life Sciences, Central South University, Changsha, Hunan, 410078, China.

出版信息

Cell Death Dis. 2019 Feb 12;10(2):137. doi: 10.1038/s41419-019-1352-4.

Long noncoding RNAs (lncRNAs) have been indicated as important regulators in various human cancers. However, the overall biological roles and clinical significance of most lncRNAs in colon carcinogenesis are not fully understood. Hence, we investigated the clinical significance, biological function and mechanism of LINC01234 in colon cancer. First, we analyzed LINC01234 alterations in colon cancer tissues and corresponding paracancerous tissues through the analysis of sequencing data obtained from The Cancer Genome Atlas and colon cancer patients. Next, we evaluated the effect of LINC01234 on colon cancer cell proliferation and its regulatory mechanism of serine hydroxymethyltransferase 2 (SHMT2) by acting as a competing endogenous RNA (ceRNA). We found that LINC01234 expression was significantly upregulated in colon cancer tissues and was associated with a shorter survival time. Furthermore, the knockdown of LINC01234 induced proliferation arrest via suppressing serine/glycine metabolism. Mechanistic investigations have indicated that LINC01234 functions as a ceRNA for miR-642a-5p, thereby leading to the derepression of its endogenous target serine hydroxymethyltransferase 2 (SHMT2). LINC01234 is significantly overexpressed in colon cancer, and the LINC01234-miR642a-5p-SHMT2 axis plays a critical role in colon cancer proliferation. Our findings may provide a potential new target for colon cancer diagnosis and therapy.

长链非编码 RNA（lncRNAs）已被证明是多种人类癌症中的重要调控因子。然而，大多数 lncRNAs 在结肠癌发生中的整体生物学作用和临床意义尚未完全阐明。因此，我们研究了 LINC01234 在结肠癌中的临床意义、生物学功能和作用机制。首先，我们通过分析来自癌症基因组图谱（TCGA）和结肠癌患者的测序数据，分析了结肠癌组织和相应癌旁组织中 LINC01234 的改变。接下来，我们通过作为竞争性内源 RNA（ceRNA）来评估 LINC01234 对结肠癌细胞增殖的影响及其对丝氨酸羟甲基转移酶 2（SHMT2）的调节机制。我们发现 LINC01234 在结肠癌组织中表达显著上调，并与较短的生存时间相关。此外，LINC01234 的敲低通过抑制丝氨酸/甘氨酸代谢诱导增殖停滞。机制研究表明，LINC01234 作为 miR-642a-5p 的 ceRNA 发挥作用，从而导致其内源性靶基因丝氨酸羟甲基转移酶 2（SHMT2）的去抑制。LINC01234 在结肠癌中显著过表达，LINC01234-miR642a-5p-SHMT2 轴在结肠癌增殖中起着关键作用。我们的研究结果可能为结肠癌的诊断和治疗提供一个潜在的新靶点。