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RNA‑binding protein quaking 5 inhibits the progression of non‑small cell lung cancer by upregulating netrin‑4
Zhuo Wu1, Shijun Liu1, Geshuo Pang1
1Department of Thoracic Surgery, Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China.
Abstract:
It was recently reported that netrin‑4 (Ntn‑4), a component of the extracellular matrix, when downregulated, is involved in the progression of several types of cancer, including breast cancer, colorectal tumours, neuroblastoma and gastric cancer. In the present study, the level of Ntn‑4 was examined in a public non‑small cell lung cancer (NSCLC) dataset from the Netherlands Cancer Institute. This analysis revealed that the mRNA expression level of Ntn‑4 was lower in the samples of patients with NSCLC compared with that in the control samples. Consistent with the mRNA level, the protein level of Ntn‑4 was also found to be decreased in NSCLC cells. However, both the function of Ntn‑4 and the underlying mechanisms of Ntn‑4 downregulation in NSCLC have yet to be fully elucidated. As was anticipated, the overexpression of Ntn‑4 led to a marked decrease in the proliferation, migration and invasion of NSCLC cells. Notably, RNA‑binding protein quaking 5 (Qki‑5) was found to exhibit antitumor activity in lung cancer, not only by enhancing the level of Ntn‑4 by binding to Ntn‑4 mRNA, but also by suppressing the proliferation, invasion and migration of NSCLC cells. However, Qki‑5 is known to be frequently downregulated in NSCLC. Moreover, the knockdown of Ntn‑4 was found to reverse the suppressive effects of Qki‑5 on NSCLC progression both in vitro and in vivo. Taken together, the findings of the present study demonstrate that Ntn‑4 is able to suppress the progression of NSCLC, and that the level of Ntn‑4 can be regulated by Qki‑5. Therefore, Ntn‑4 may be a novel diagnostic and therapeutic target for the treatment of NSCLC.
Insights
Netrin-4 (Ntn-4) suppresses non-small cell lung cancer (NSCLC) progression by reducing cell proliferation and invasion. RNA-binding protein Quaking 5 (Qki-5) enhances Ntn-4 levels, offering a potential therapeutic target for NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Extracellular Matrix Research
Background:
- Netrin-4 (Ntn-4), an extracellular matrix component, is implicated in the progression of various cancers.
- Downregulation of Ntn-4 is observed in several cancer types, but its role in non-small cell lung cancer (NSCLC) requires further investigation.
- The mechanisms underlying Ntn-4's function and regulation in NSCLC are not fully understood.
Purpose of the Study:
- To investigate the expression levels and functional role of Netrin-4 (Ntn-4) in non-small cell lung cancer (NSCLC).
- To elucidate the regulatory relationship between RNA-binding protein Quaking 5 (Qki-5) and Ntn-4 in NSCLC.
- To explore the potential of Ntn-4 as a diagnostic and therapeutic target for NSCLC.
Main Methods:
- Analysis of Ntn-4 mRNA and protein levels in NSCLC patient samples and cell lines.
- In vitro and in vivo experiments assessing the effects of Ntn-4 overexpression and knockdown on NSCLC cell behavior.
- Investigation of Qki-5's interaction with Ntn-4 mRNA and its impact on NSCLC progression.
Main Results:
- Ntn-4 expression (mRNA and protein) was significantly decreased in NSCLC samples compared to controls.
- Overexpression of Ntn-4 suppressed NSCLC cell proliferation, migration, and invasion.
- Qki-5 was found to enhance Ntn-4 levels by binding to its mRNA, exhibiting antitumor activity in NSCLC; however, Qki-5 itself is downregulated in NSCLC.
- Knockdown of Ntn-4 reversed the suppressive effects of Qki-5 on NSCLC progression.
Conclusions:
- Ntn-4 demonstrates a tumor-suppressive role in NSCLC progression.
- Qki-5 regulates Ntn-4 levels, suggesting a coordinated mechanism in controlling NSCLC.
- Ntn-4 represents a promising novel diagnostic and therapeutic target for NSCLC treatment.
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