Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Emergency Medicine, Jiangyin People's Hospital, Jiangyin, Jiangsu, China.
J Int Med Res. 2021 May;49(5):3000605211004414. doi: 10.1177/03000605211004414.
To examine the role of the long noncoding RNA LINC01296 in colorectal carcinoma (CRC) and to explore the underlying mechanism.
We detected LINC01296 expression levels in a cohort of 51 paired CRC and normal tissues. We also assessed the effects of LINC01296 on cell proliferation and apoptosis in CRC cells , and measured its effect on tumor growth in an mouse model. We identified the potential downstream targets of LINC01296 and assessed its regulatory effects.
Expression levels of LINC01296 were elevated in 37/51 CRC tissues compared with the corresponding normal tissues and were significantly associated with tumor stage, lymph node metastasis, and distant metastasis. Knockdown of LINC01296 using antisense oligonucleotides inhibited cell proliferation and promoted apoptosis of colon cancer cells and inhibited tumor growth . Knockdown of LINC01296 also significantly increased the gene expression of p15 in colon cancer cells. LINC01296-specific suppression of p15 was validated by the interaction between enhancer of zeste homolog 2 and LINC01296.
Overexpression of LINC01296 suppressed the expression of p15 leading to CRC carcinogenesis. These findings may provide the basis for novel future CRC-targeted therapies.
研究长链非编码 RNA LINC01296 在结直肠癌(CRC)中的作用,并探讨其潜在的作用机制。
我们检测了 51 对 CRC 组织和相应正常组织中 LINC01296 的表达水平。我们还评估了 LINC01296 对 CRC 细胞增殖和凋亡的影响,并在小鼠模型中测量了其对肿瘤生长的影响。我们鉴定了 LINC01296 的潜在下游靶标,并评估了其调控作用。
与相应的正常组织相比,37/51 例 CRC 组织中 LINC01296 的表达水平升高,且与肿瘤分期、淋巴结转移和远处转移显著相关。用反义寡核苷酸敲低 LINC01296 抑制了结肠癌细胞的增殖和促进了细胞凋亡,并抑制了肿瘤生长。LINC01296 的敲低还显著增加了结肠癌细胞中 p15 的基因表达。通过 EZH2 和 LINC01296 之间的相互作用验证了 LINC01296 对 p15 的特异性抑制。
LINC01296 的过表达抑制了 p15 的表达,导致 CRC 发生癌变。这些发现可能为未来针对 CRC 的新型靶向治疗提供依据。