hsa-miR-125a-3p 和 hsa-miR-125a-5p 在非小细胞肺癌中下调，对肺癌细胞的侵袭和迁移有相反的影响。

BACKGROUND: Two mature microRNAs (miRNAs), hsa-miR-125a-3p and hsa-miR-125a-5p (collectively referred to as hsa-miR-125a-3p/5p), are derived from 3' and 5' ends of pre-miR-125a, respectively. Although impaired regulation of hsa-miR-125a-5p has been observed in some tumors, the role of this miRNA in invasion and metastasis remains unclear, and few studies have examined the function of hsa-miR-125a-3p. In order to characterize the functions of hsa-miR-125a-3p/5p in invasion and metastasis of non-small cell lung cancer (NSCLC), we investigated the relationships between hsa-miR-125a-3p/5p expression and lymph node metastasis in NSCLC tissues. We also explored the impact of expression of these miRNAs on invasive and migratory capabilities of lung cancer cells. METHODS: Expression of hsa-miR-125a-3p/5p in NSCLC tissues was explored using real-time PCR. The relationships between hsa-miR-125a-3p/5p expression and pathological stage or lymph node metastasis were assessed using the Spearman correlation test. For in vitro studies, lung cancer cells were transfected with sense and antisense 2'-O-methyl oligonucleotides for gain-of-function and loss-of-function experiments. Transwell experiments were performed to evaluate cellular migration and invasion. RESULTS: Expression of hsa-miR-125a-3p/5p was lower in NSCLC tissues than in adjacent normal lung tissues (LAC). Furthermore, the results from the Spearman correlation test showed a negative relationship between hsa-miR-125a-3p expression and pathological stage or lymph node metastasis and an inverse relationship between hsa-miR-125a-5p expression and pathological stage or lymph node metastasis. In vitro gain-of-function experiments indicated that hsa-miR-125a-3p and hsa-miR-125a-5p function in an opposing manner, suppressing or enhancing cell migration and invasion in A549 and SPC-A-1 cell lines, respectively. These opposing functions were further validated by suppression of hsa-miR-125a-3p and hsa-miR-125a-5p expression in loss-of-function experiments. CONCLUSION: Hsa-miR-125a-3p and hsa-miR-125a-5p play distinct roles in regulation of invasive and metastatic capabilities of lung cancer cells, consistent with the opposing correlations between the expression of these miRNAs and lymph node metastasis in NSCLC. These results provide new insights into the roles of miR-125a family members in the development of NSCLC.

背景：两个成熟的 microRNA（miRNA），hsa-miR-125a-3p 和 hsa-miR-125a-5p（统称为 hsa-miR-125a-3p/5p），分别来自 pre-miR-125a 的 3' 和 5' 端。尽管已经观察到 hsa-miR-125a-5p 在某些肿瘤中的调节受损，但该 miRNA 在侵袭和转移中的作用仍不清楚，并且很少有研究检测 hsa-miR-125a-3p 的功能。为了描述 hsa-miR-125a-3p/5p 在非小细胞肺癌（NSCLC）侵袭和转移中的功能，我们研究了 hsa-miR-125a-3p/5p 表达与 NSCLC 组织中淋巴结转移之间的关系。我们还探讨了这些 miRNA 表达对肺癌细胞侵袭和迁移能力的影响。

方法：使用实时 PCR 研究 NSCLC 组织中 hsa-miR-125a-3p/5p 的表达。使用 Spearman 相关检验评估 hsa-miR-125a-3p/5p 表达与病理分期或淋巴结转移之间的关系。在体外研究中，用 sense 和 antisense 2'-O-甲基寡核苷酸转染肺癌细胞进行功能获得和功能丧失实验。进行 Transwell 实验以评估细胞迁移和侵袭。

结果：与相邻正常肺组织（LAC）相比，NSCLC 组织中 hsa-miR-125a-3p/5p 的表达较低。此外，Spearman 相关检验的结果显示 hsa-miR-125a-3p 表达与病理分期或淋巴结转移呈负相关，hsa-miR-125a-5p 表达与病理分期或淋巴结转移呈负相关。体外功能获得实验表明，hsa-miR-125a-3p 和 hsa-miR-125a-5p 以相反的方式发挥作用，分别抑制或增强 A549 和 SPC-A-1 细胞系的细胞迁移和侵袭。在功能丧失实验中通过抑制 hsa-miR-125a-3p 和 hsa-miR-125a-5p 的表达进一步验证了这些相反的功能。

结论：hsa-miR-125a-3p 和 hsa-miR-125a-5p 在调节肺癌细胞侵袭和转移能力方面发挥不同的作用，与这些 miRNA 的表达与 NSCLC 淋巴结转移之间的相反相关性一致。这些结果为 miR-125a 家族成员在 NSCLC 发展中的作用提供了新的见解。