KIAA0101

Official Full Name

PCNA clamp associated factor

Organism

Homo sapiens

GeneID

9768

Background

Enables chromatin binding activity and molecular adaptor activity. Involved in several processes, including DNA metabolic process; centrosome cycle; and response to UV. Located in centrosome; nucleus; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

PCLAF; L5; PAF; OEATC; PAF15; OEATC1; p15PAF; NS5ATP9; OEATC-1; p15/PAF; KIAA0101; p15(PAF);

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Detailed Information

KIAA0101, also known as PAF15 (antigen-associated factor with unclear proliferating cells), encodes a PCNA (proliferating cell nuclear antigen)-associated factor. KIAA0101 is a positive, but not previously recognized, regulatory factor for ccRCC ( Renal clear cell carcinoma) proliferation and migration induced by recombinant human erythropoietin (r-Hu EPO). KIAA0101 is reported to be an APC/C (Ubiquitin ligase) regulatory protein involved in cell cycle progression, DNA repair and injury response.

The KIAA0101 protein is a negative regulator of cancer progression. Zhu et al. found protein levels of KIAA0101 were up-regulated in 61 human primary cancer tissues from patients with gastric cancer. In addition, overexpression of KIAA0101 also indicates poor prognosis in lung cancer patients. The mRNA level of KIAA0101 is much higher in primary tumors of patients with kidney, breast, liver and pancreatic cancers. Clinical survival analysis also showed that low levels of KIAA0101 were associated with prolonged survival. KIAA1010 also has been seen to promote the transformation of mouse fibroblast NIH3T3 cells into tumor in vivo and involved as a marker in relapse of gastric cancer. In addition, the level of KIAA0101 was also found to be upregulated in cancer tissues from esophageal cancer, gastric cancer and lung cancer. KIAA0101 also plays an adverse role in the mechanism by which EPO (Erythropoietin) triggers adverse reactions. Inhibition of KIAA0101 in cancer cells improves cancer cells that are sensitive to ultraviolet light. Hsa-miR-429 can exert tumor suppressor effects in STS by targeting KIAA0101, thereby regulating metastatic characteristics such as proliferation, migration, anchoring independent growth and invasion.

KIAA0101 has two main transcript variants (television), designated KIAA0101 tv1 and tv2. KIAA0101 tv1 promotes cell survival by inhibiting p53 in HCC cells (liver cancer cells). Compared to NT (non-tumorous liver tissue), KIAA0101 tv1 is overexpressed in HCC, particularly in late HCC. KIAA0101 tv1 promotes proliferation, colony formation and tumor xenografting of NIH3T3 cells in nude mice. It also protects cells from doxorubicin-induced apoptosis. Compared to HCC, KIAA0101 tv2 is overexpressed in NT and exerts different expression patterns from KIAA0101 tv1 in HCC tissues. It has tumor suppressing properties and inhibits the expression and function of KIAA0101 tv1 in HCC, similar to KIAA0101 tv1 shRNA. Therefore, KIAA0101 tv2 can be used as a competitor of KIAA0101 tv1 to suppress the malignant characteristics of KIAA0101 tv1 in HCC development.

KIAA0101 is also essential for the migration and chemical resistance of EOC cells, which are mediated by Wnt/[beta]-catenin signaling. KIAA0101 is directly regulated by miR-429. However, it is worth noting that miRNAs typically have multiple targets. KIAA0101, which is targeted by miR-429, promotes invasion and chemical resistance of EOC cells via the Wnt/β-catenin signaling pathway. Both miR-429 and KIAA0101 can be used to predict the prognosis of EOC patients and can represent new therapeutic targets for EOC. KIAA0101 is also involved in the proliferation, migration and anchorage-independent growth of metastatic fibrosarcoma cells, and miR-429 inhibits these processes by post-transcriptional targeting of KIAA0101. MiR-429 has an anti-metastatic effect that mediates and promotes tumor progression by targeting KIAA0101 to promote gene transfer. Overexpression of miR-429 inhibits KIAA0101 in mRNA and protein levels.

The miR-183 acts as an anti-proliferative gene by directly targeting KIAA0101, which is involved in cell cycle activation and inhibition of p53–p21-mediated cell cycle arrest. In vitro, miR-183 decreases the expression of KIAA0101 at both the mRNA and protein levels by directly binding to the 3′-UTR. KIAA0101 is overexpressed in aggressive vs. non-aggressive PRL tumors, and moreover, KIAA0101 expression is significantly correlated with Ki-67 and p53 labeling. The miR-183-mediated KIAA0101 silencing decreases HeLa and ZR-75-1 proliferation by deregulating cell cycle progression.

References:

Chen H, et al. KIAA0101, a target gene of miR-429, enhances migration and chemoresistance of epithelial ovarian cancer cells. Cancer Cell International, 2016, 16(1).
Fan S, et al. KIAA0101 is associated with human renal cell carcinoma proliferation and migration induced by erythropoietin. Oncotarget, 2016, 7(12):13520-13537.
Samantarrai D, et al. miR-429 inhibits metastasis by targeting KIAA0101 in Soft Tissue Sarcoma. Experimental Cell Research, 2017, 357(1).
Roche M, et al. "Deregulation of miR-183 and KIAA0101 in Aggressive and Malignant Pituitary Tumors." Frontiers in Medicine 2(2015):54.

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