| [1] PubMed ID: | 35526007 |
| Disease Name: | Carcinoma, Non-Small-Cell Lung |
| Tissue: | Lung |
| Dysfunction Pattern: | N/A |
| Validated Method: | qRT-PCR/FISH/CCK-8 assay/RIP//High-throughput sequencing |
| Description: | The molecular mechanisms by which tRFs exert their functions are largely unclear. Prior studies have shown that some tRFs can directly bind to the 3′ untranslated regions (3′ UTRs) of target mRNAs, leading to translation suppression [18, 19]. Other tRFs repressed the stability of oncogenes by replacing the 3′-UTR of mRNAs. For instance, hypoxia-induced i-tRFs could decrease the stability of some oncogenes via YBX1 replacement [10]. tRFs could also bind to mRNA 3′-UTR and induce its degradation, resulting in decreased protein production [12]. More recently, it was reported that certain tRFs could bind to proteins and alter the phosphorylation status and the function of the target protein [20]. The present study demonstrated, for the first time to our knowledge, that tRFs (i.e., AS-tDR-007333) interacted with binding protein to modify histone modifications and activate transcription factor to enhance promoter activity, resulting in gene expression alteration. These findings expand our knowledge on the regulatory roles of tRFs in cancer cells. |
| Comparision: | Disease VS Control |
| Mechanism: | We found that AS-tDR-007333 directly bound to HSPB1 with high specificity in NSCLC cells. The HSPB1 (HSP27) is a member of the highly conserved heat shock proteins (HSPs) which are expressed at low levels under normal conditions, but induced in response to cellular stresses, including heat shock, hypoxia, genotoxic agents, and overexpression of oncoproteins [21]. Previous studies showed that HSPB1 was highly expressed in a variety of human cancers, including lung cancer [22]. Overexpression of HSPB1 was associated with malignant properties of cancer cells, resistance to chemotherapy or radiotherapy, and poor prognosis [14,聽23]. HSPB1 also increased cell proliferation by facilitating cell cycle progression [24], promoting migration and invasion [25], maintaining cancer stem cells [26], or inactivating the Hippo tumor suppressor pathway [27]. Nevertheless, the molecular mechanisms governing HSPB1 expression were unclear. Here, we showed that HSPB1 bound to and activated by AS-tDR-007333. Rescue assays showed that the impact of AS-tDR-007333 on cell proliferation is dependent, at least in part, on HSPB1. These results revealed a novel mechanism by which tRF interacted with HSPB1 to regulate NSCLC cell proliferation. |
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