Chinese researchers discovered novel non-small cell lung cancer therapy targets

Author Xuebing Li

The most prevalent type of lung cancer is non-small cell lung cancer (NSCLC). The clinical application of targeted medicines has accelerated the advancement of NSCLC treatment. Nevertheless, the prognosis of NSCLC patients is still poor because of the late detection and increased risk of spread of cancer cells. Finding effective molecular targets for NSCLC cell growth, migration, and invasion is therefore necessary.

In recent years, protein ubiquitin ligase as well as deubiquitinase-induced ubiquitination and deubiquitination processes have been emphasized in anticancer and cancer-causing functions. In previous studies, it was shown that a special type of this protein, OTU deubiquitinase (OTUD5), is downregulated in NSCLC cells. After its upregulation, cell proliferation, migration and invasion were found to be suppressed. Researchers from the Capital Medical University found that this suppression was regulated through the OTUD5-meditated deubiquitination process to stabilize enzyme phosphatase and tensin homolog protein (PTEN). Furthermore, they illustrated that upstream of OTUD5 was negatively regulated by microRNA miR-652-3p.

The results led researchers to conclude the involvement of miR-652-3p, OTUD5 and PTEN in proliferation, migration and invasion of NSCLC cells, and targeting them may inhibit NSCLC progression and provide new target options for NSCLC treatment.

最普遍的肺癌類型是非小細胞肺癌(NSCLC)。靶向藥物的臨床應用加速了NSCLC治療的進步。然而,由於發現晚和癌細胞擴散的風險增加,NSCLC患者的預後仍然很差。因此,有必要為 NSCLC 細胞的生長、遷移和侵襲尋找有效的分子靶點。

近年來,蛋白質泛素連接酶以及去泛素酶誘導的泛素化和去泛素化過程在抗癌和致癌功能中受到重視。在先前的研究中,表明這種蛋白質的一種特殊類型 OTU 去泛素酶 (OTUD5) 在 NSCLC 細胞中被下調。在其上調後,發現細胞增殖、遷移和侵襲受到抑制。首都醫科大學的研究人員發現,這種抑制是通過 OTUD5 介導的去泛素化過程來調節的,以穩定酶磷酸酶和張力蛋白同源蛋白 (PTEN)。此外,他們說明 OTUD5 的上游受到 microRNA miR-652-3p 的負調控。

該結果使研究人員得出結論,miR-652-3p、OTUD5和PTEN參與NSCLC細胞的增殖、遷移和侵襲,靶向它們可能抑制NSCLC進展,為NSCLC治療提供新的靶點選擇。

 

Reference: Li X, Lu B, Zhang L, Yang J, Cheng Y, Yan D. Mechanism of OTUD5 in non‐small cell lung cancer cell proliferation, invasion, and migration. Bosn J of Basic Med Sci [Internet]. 2022Jun.27 [cited 2022Jul.3];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/7206

Editor: Merima Bukva, MPharm

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