FAM120A

Official Full Name

family with sequence similarity 120 member A

Organism

Homo sapiens

GeneID

23196

Background

Enables RNA binding activity. Located in cytosol. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

OSSA; C9orf10; HBVPTPAP;

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Detailed Information

FAM120A as an oxidative stress-associated Src activator can be also called c9orf10 or OSSA. FAM120A plays important role in the activation and recruitment of proteins involved in IL13Rα2 signalings, such as FAK, Src, PI3K, and other proteins.

FAM120A associated with the activation of IL-13 receptor α2 signaling

Interleukin 13 (IL-13) has been demonstrated to play key roles in different pathological diseases including asthma, autoimmune diseases, ulcerative colitis, and so on. IL-13 signaling based on interleukin-13 receptor subunit alpha-2 (IL13Rα2) has been proved to be associated with the significant increase of cell adhesion, migration, and invasion of colorectal cancer cells during the process of colon cancer invasion and liver metastasis. However, the mechanism of this phenomenon has not been fully explained.

The molecular partners of IL13Rα2 and the mechanisms have been identified by Casal’s group using immunoprecipitation experiments in combination with a proteomic approach. In their study, they found that FAM120A as a scaffold protein is one of the molecular partners of IL13Rα2, which is involved in signal transduction. Fam120a is overexpressed in cell lines of human colon cancer and can regulate signal network association of IL13Rα2 activity, including FAK, PI3K, G protein-coupled receptor, SRC, and TRAIL receptor. In addition, FAM120A is associated with dynein and motor protein which is related to cargo transportation. The activation of FAK and PI3K/Akt/mTOR pathway caused by IL13Rα2 is mediated by FAM120A. IL13Rα2 also recruits PI3K which acts as a scaffold protein phosphorylates and activates PI3K through Src family kinases. FAM120A silencing eliminates cell migration, invasion, and survival induced by IL-13. In the end, liver colonization and metastasis in nude mice or mice can be prevented by the antibody-blocked IL13Rα2 or FAM120A silencing. All the experiments proved that the FAM120A protein in IL-13/IL13Rα2 signaling pathway is a key mediator of colon cancer invasion and liver metastasis.

The important role of CircFAM120A in disease

Circular RNA (circrna), as a kind of endogenous RNA that is non-coding, is mainly existed in cytoplasm and exosomes. Accumulated studies have exhibited that circRNAs take part in both physiological and pathological processes via multiple actions. For example, circRNAs bind to other ribonucleic acids (mRNA and miRNA) as a molecular sponge. The phenotypical changes of the cell can be also dynamically reflected by CircRNA profiles. CircFAM120A, located at chromosome 1q21, is derived from FAM120A and is composed of three exons. CircFAM120A has been proved to be related to many diseases. Cheng et al. identified circFAM120A as a potential biomarker for lung cancer hypoxia using qRT-PCR. They demonstrated that circFAM120A was a circular RNA instead of a liner RNA. Meanwhile, they also explored the splicing site of circFAM120A by sanger sequencing. It is noted that circFAM120A mainly exists in the cytosol rather than the nucleus. Importantly, they also revealed the decreased expression levels of CircFAM120A after treatment with hypoxia. The research carried out by cheng et al. is hopeful to provide new evidence to explain the mechanism of hypoxia-induced lung cancer metastasis, and promote clinical treatment by monitoring the degree of tumor hypoxia.

FAM120A Figure 1. Proteins coimmunoprecipitated with FAM120A (Bartolomé et al., 2015).

References:

Kelly T J, Suzuki H I, Zamudio J R, et al. Sequestration of microRNA-mediated target repression by the Ago2-associated RNA-binding protein FAM120A. RNA, 2019, 25(10): 1291-1297.
Bartolomé R A, García-Palmero I, Torres S, et al. IL13 receptor α2 signaling requires a scaffold protein, FAM120A, to activate the FAK and PI3K pathways in colon cancer metastasis. Cancer research, 2015, 75(12): 2434-2444.
Ma J, Meng Q, Zhan J, et al. Paeoniflorin Suppresses Rheumatoid Arthritis Development via Modulating the Circ-FAM120A/miR-671-5p/MDM4 Axis. Inflammation, 2021: 1-14.

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