Study identifies C1orf122 as prognostic marker in liver cancer

Primary liver cancer is the third leading cause of cancer-related deaths, of which hepatocellular carcinoma (HCC) accounts for approximately 90% of all liver cancer cases. Given that the development of HCC is a multifactorial and multistage process, its increasing incidence underscores the need to understand its molecular mechanisms and identify potential biomarkers and therapeutic targets.

Previous studies have implicated chromosome 1 open reading frame 122 (C1orf122), a protein-coding gene, in the pathogenesis of multiple cancers, including HCC. Overexpression of C1orf122 is associated with HCC progression and poor prognosis; however, the mechanisms underlying its tumorigenic role in HCC remain elusive.

A recent study published in the Genes & Diseases journal by researchers from Harbin Medical University, Bishan Hospital of Chongqing Medical University, and Chongqing Medical University elucidates the molecular mechanisms underlying the tumorigenic role of C1orf122 in HCC.

A pan-cancer analysis using the TCGA database and subsequent experimental validation revealed that the expression of C1orf122 was higher in HCC tissues compared to normal tissues, and that HCC patients with C1orf122 overexpression had a worse overall survival index, suggesting that C1orf122 contributes to HCC progression and may serve as a novel independent prognostic marker for HCC.

Knockdown of C1orf122 significantly reduced the viability and proliferation of HepG2 and HuH-7 cells, whereas overexpression of C1orf122 mediated the opposite effect. The authors observed that C1orf122 promotes cell growth by inhibiting apoptosis, as evidenced by a decline in pro-apoptotic markers (Bax and cleaved-caspase-3), and an upregulation of anti-apoptotic markers such as total Bcl-2 protein, upon C1orf122 overexpression. Furthermore, increased expression of epithelial-to-mesenchymal transition (EMT) markers (N-Cadherin, Vimentin, Slug, and Twist1) upon C1orf122 overexpression establishes that C1orf122 exerts its oncogenic effects in HCC by enhancing cell proliferation, suppressing apoptosis, and facilitating cell migration.

Mechanistically, C1orf122 interacts with SRPK1 and mediates its phosphorylation at the Thr601 site via mTOR kinase, which subsequently activates the PI3K/AKT/GSK3β signaling pathway, resulting in HCC onset and progression.

In conclusion, the findings of this study elucidate the tumorigenic role of C1orf122 in HCC and show that C1orf122 promotes HCC via the SRPK1-PI3K/AKT/GSK3β axis, highlighting its potential as a diagnostic and therapeutic target for HCC.