Lamin A/C proteins, major components of the nuclear lamina, are encoded by the LMNA gene. These proteins have multiple cellular functions, including DNA transcription and replication, chromatin organization, regulation of the cell cycle, and apoptosis. Mutations in LMNA are associated with a variety of diseases called laminopathies. LMNA has implications in cancer; however, its mechanisms of dysregulation in cancer cells are not yet fully understood. In this study, among the LMNA transcript variants, we focused on a transcriptional variant 6 (termed LMNA-V6), which contains unique 3 exons upstream of exon 1 of LMNA. The promoter region of LMNA-V6 formed multiple G-quadruplexes and increased its transcriptional activity. Moreover, LMNA-V6 negatively regulated other LMNA mRNA variants, lamin A and lamin C, via direct interaction with their promoter. Knockdown of LMNA-V6 decreased the proliferation of colon cancer cells, whereas overexpression of the unique 3 exons of LMNA-V6 increased cell growth. Furthermore, microarray gene expression profiling showed that alteration of LMNA-V6 levels influenced the expression of p53 in colon cancer cells. Taken together, the results suggest that LMNA-V6 may be a novel functional RNA whose expression is regulated through multiple G-quadruplexes in colon cancer cells.

Lamin A/C 蛋白是核层的主要成分，由LMNA基因编码。这些蛋白质具有多种细胞功能，包括 DNA 转录和复制、染色质组织、细胞周期调节和细胞凋亡。LMNA突变与多种称为椎板病的疾病有关。LMNA对癌症有影响；然而，其在癌细胞中失调的机制尚未完全了解。在这项研究中，在LMNA转录变体中，我们专注于转录变体 6（称为LMNA-V6），它包含LMNA外显子 1 上游的独特 3 个外显子。LMNA-V6启动子区形成多个 G-四链体并增加其转录活性。此外，LMNA-V6通过与其启动子的直接相互作用对其他LMNA mRNA 变体lamin A和lamin C进行负调节。LMNA-V6 的敲低降低了结肠癌细胞的增殖，而LMNA-V6独特的 3 个外显子的过度表达增加了细胞生长。此外，微阵列基因表达谱显示LMNA-V6水平的改变影响了结肠癌细胞中 p53 的表达。综上所述，结果表明LMNA-V6 可能是一种新型功能性 RNA，其表达通过结肠癌细胞中的多个 G-四链体进行调节。