Kinesin Family Member C1 Overexpression Exerts Tumor-Promoting Properties in Head and Neck Squamous Cell Carcinoma via the Rac1/Wnt/β-catenin Pathway

Kinesin family member C1 (KIFC1) is a kinesin 14 motor protein, and its abnormal upregulation promotes the malignant behavior of cancer cells. N6-methyladenosine (m6A) RNA methylation is a common modification of eukaryotic messenger RNA and affects RNA expression. In this study, we explored how KIFC1 regulated head and neck squamous cell carcinoma (HNSCC) tumorigenesis and how m6A modification affected KIFC1 expression. A bioinformatics analysis was performed to screen for genes of interest, and in vitro and in vivo studies were carried out to investigate the function and mechanism of KIFC1 in HNSCC tissues. We observed that the expression of KIFC1 in HNSCC tissues was significantly higher than that in normal or adjacent normal tissues. Patients with cancer with higher KIFC1 expression have a lower tumor differentiation status. Demethylase alkB homolog 5, a cancer-promoting factor in HNSCC tissues, could interact with KIFC1 messenger RNA and posttranscriptionally activate KIFC1 through m6A modification. KIFC1 downregulation suppressed HNSCC cell growth and metastasis in vivo and in vitro. However, overexpression of KIFC1 promoted these malignant behaviors. We demonstrated that KIFC1 overexpression activated the oncogenic Wnt/β-catenin pathway. KIFC1 interacted with the small GTPase Ras-related C3 botulinum toxin substrate 1 (Rac1) at the protein level and increased its activity. The Rho GTPase Rac1 was indicated to be an upstream activator of the Wnt/β-catenin signaling pathway, and its Rac1 inhibitor, NSC-23766, treatment reversed the effects caused by KIFC1 overexpression. Those observations demonstrate that abnormal expression of KIFC1 may be regulated by demethylase alkB homolog 5 in an m6A-dependent manner and promote HNSCC progression via the Rac1/Wnt/β-catenin pathway.

 

Comments:

The study you described focuses on the role of Kinesin family member C1 (KIFC1) in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and how its expression is regulated by N6-methyladenosine (m6A) RNA methylation.

The researchers first performed a bioinformatics analysis to identify genes of interest in HNSCC. They found that the expression of KIFC1 in HNSCC tissues was significantly higher compared to normal or adjacent normal tissues. Furthermore, patients with higher KIFC1 expression tended to have a lower tumor differentiation status, indicating a correlation between KIFC1 expression and cancer aggressiveness.

The study also investigated the mechanism behind the upregulation of KIFC1 in HNSCC. They discovered that a demethylase called alkB homolog 5 (ALKBH5), known to promote cancer in HNSCC tissues, interacted with KIFC1 messenger RNA (mRNA) and posttranscriptionally activated KIFC1 through m6A modification. This suggests that abnormal m6A modification mediated by ALKBH5 contributes to the elevated expression of KIFC1 in HNSCC.

To understand the functional impact of KIFC1 in HNSCC, the researchers conducted in vitro and in vivo experiments. They observed that downregulation of KIFC1 suppressed HNSCC cell growth and metastasis, while overexpression of KIFC1 promoted these malignant behaviors. This indicates that KIFC1 plays a crucial role in promoting HNSCC progression.

Further investigation revealed that KIFC1 overexpression activated the Wnt/β-catenin pathway, which is known to be oncogenic. KIFC1 was found to interact with a small GTPase called Rac1 at the protein level and enhance its activity. Rac1 is an upstream activator of the Wnt/β-catenin signaling pathway. To validate the involvement of Rac1 in KIFC1-mediated effects, the researchers used a Rac1 inhibitor called NSC-23766, which reversed the effects caused by KIFC1 overexpression. This suggests that KIFC1 promotes HNSCC progression through the Rac1/Wnt/β-catenin pathway.

In summary, this study demonstrates that the abnormal expression of KIFC1 in HNSCC is regulated by ALKBH5-mediated m6A modification. Elevated KIFC1 expression promotes HNSCC progression by activating the Rac1/Wnt/β-catenin pathway. These findings provide insights into the molecular mechanisms underlying HNSCC tumorigenesis and highlight potential therapeutic targets for this type of cancer.