非小细胞肺癌的预后不良主要归因于低效的诊断和顽强的耐药性。因此，鉴定癌细胞对现有治疗的敏感性的新的分子决定因子对于开发新的有效联合治疗策略尤为重要。微小RNA（miRNA）是一类小型非编码RNA，已被确定为调控多种细胞过程的主要调节因子，其在肿瘤起始、进展和转移中起关键作用。这一特点以及它们在许多不同癌症中的广泛失调，引发了人们对miRNA作为癌症治疗的新的治疗靶点的热情，尤其是对于携带KRAS突变的难治性癌症的患者。在本研究中，我们采用功能丧失筛选方法，鉴定了对顺铂敏感性促进肺腺癌（LUAD）细胞的miRNA沉默。我们的结果特别显示，针对靶向miR-92a-3p（一个的miR-17 ~ 92簇的成员）的反义寡核苷酸最大程度地增加了KRAS突变LUAD细胞对顺铂的敏感性。此外，我们还证明了这种miRNA对具有不同遗传改变的各种肿瘤细胞系的凋亡阈值和增殖能力的精细调控作用。综上所述，这些数据表明针对miR-92a-3p的靶向治疗可能是克服实体瘤治疗耐药性的有效策略。© 2023. 作者。

Non-small cell lung cancer is characterized by a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Therefore, the identification of new molecular determinants underlying sensitivity of cancer cells to existing therapy is of particular importance to develop new effective combinatorial treatment strategy. MicroRNAs (miRNAs), a class of small non-coding RNAs, have been established as master regulators of a variety of cellular processes that play a key role in tumor initiation, progression and metastasis. This, along with their widespread deregulation in many distinct cancers, has triggered enthusiasm for miRNAs as novel therapeutic targets for cancer management, in particular in patients with refractory cancers such as those harboring KRAS mutations. In this study, we performed a loss-of-function screening approach to identify miRNAs whose silencing promotes sensitivity of lung adenocarcinoma (LUAD) cells to cisplatin. Our results showed in particular that antisense oligonucleotides directed against miR-92a-3p, a member of the oncogenic miR-17 ~ 92 cluster, caused the greatest increase in the sensitivity of KRAS-mutated LUAD cells to cisplatin. In addition, we demonstrated that this miRNA finely regulates the apoptotic threshold and the proliferative capacity of various tumor cell lines with distinct genetic alterations. Collectively, these data suggest that targeting miR-92a-3p may serve as an effective strategy to overcome treatment resistance of solid tumors.© 2023. The Author(s).