A single circular RNA molecule is emerging as a common thread running through nine different cancers. In a review published in the journal Cell Division, researchers led by Yan Lv, Dan Li and Qun-Xian Zhang compiled evidence that Hsa_circ_0000285, a recently discovered circular RNA, is abnormally expressed in hepatocellular carcinoma, gastric cancer, bladder cancer, nasopharyngeal carcinoma, osteosarcoma, thyroid cancer, glioma, cervical cancer and neuroblastoma, predominantly as an overexpression. The authors argue that this pattern of abnormal expression is significantly associated with cancer cell growth, metastasis and poor prognosis in patients, positioning circ_0000285 as a candidate target molecule for future cancer treatment.
Circular RNAs are a distinctive class of non-coding RNA molecules. Unlike conventional linear RNAs, they form a closed circular structure, which makes them exceptionally stable inside cells. Their best-characterized function is to act as sponges for microRNAs, the short RNA fragments that normally suppress the expression of downstream target genes. By binding and sequestering these microRNAs, circular RNAs relieve the inhibitory pressure on target genes, and in cancer that relief can translate into uncontrolled cell growth and spread. The review notes that circ_0000285 follows this playbook, sponging miR-582-3p, miR-1278, miR-409-3p, miR-599, miR-127-5p, miR-654-3p and miR-197-3p to promote the expression of downstream target genes, or in some settings directly regulating target gene expression.
The expression data compiled by the authors show a striking tissue-specific split. Circ_0000285 is significantly overexpressed in hepatocellular carcinoma, gastric cancer, nasopharyngeal carcinoma, osteosarcoma, thyroid cancer, glioma, cervical cancer and neuroblastoma tissues or serum, with overexpression documented across a long list of cell lines, including Hep 3B, Huh7 and SNU-182 in liver cancer; HGC-27, AGS and GTL-16 in gastric cancer; HK-1, C666-1, 5-8F and SUNE-1 in nasopharyngeal carcinoma; SJSA1, U2OS, Saos2, MG63 and HOS in osteosarcoma; KTC-1, TPC-1, SW579 and FTC133 in thyroid cancer; SHG-44, U251 and A172 in glioma; HeLa, SiHa, C4-1, C-33a and CaSki in cervical cancer; and SK-N-BE, SK-N-SH, SK-N-AS and IMR-32 in neuroblastoma. Bladder cancer is the exception: in bladder tumor tissues and in the cell lines HTB-9, T24, J82, SW780, RT4 and the cisplatin-resistant RT4/DDP, expression of circ_0000285 is significantly suppressed rather than elevated.
Functional experiments reviewed by the team link that overexpression to aggressive cellular behavior. In hepatocellular carcinoma, gastric cancer, thyroid cancer, neuroblastoma and nasopharyngeal carcinoma cell lines, overexpression of circ_0000285 promotes cell proliferation while inhibiting apoptosis, the programmed cell death that normally restrains tumor expansion. In nasopharyngeal carcinoma cells it drives clonogenic formation, the ability of single cells to seed colonies, and in glioma cells it enhances proliferative capacity. In osteosarcoma and cervical cancer cells, overexpression promotes proliferation, clonogenic formation and cell cycle transition while suppressing apoptosis. The authors also report that overexpression facilitates migration in liver, osteosarcoma, thyroid, glioma, cervical cancer and neuroblastoma cells, and invasion in nasopharyngeal carcinoma, gastric cancer, osteosarcoma, glioma and cervical cancer cells, the two capabilities that allow a tumor to break free of its original site and colonize distant tissue.
Animal experiments reinforce the in vitro findings. When circ_0000285 was overexpressed, tumorigenic capability, the ability to form tumors, increased in nude mice implanted with Hep3B liver cancer cells, HGC-27 and GTL-16 gastric cancer cells, C666-1 nasopharyngeal carcinoma cells, U2OS and MG63 osteosarcoma cells, KTC-1 thyroid cancer cells, SHG-44 glioma cells, C-33a and HeLa cervical cancer cells, and SK-N-BE neuroblastoma cells. Taken together, the review concludes that overexpression of circ_0000285 signals enhanced capabilities in cancer growth and metastasis, which in turn points toward poor prognosis for patients whose tumors carry high levels of the molecule.
One of the most detailed mechanisms comes from hepatocellular carcinoma. The review describes work showing that circ_0000285 and the cell-cycle gene CCNB2 are upregulated in liver cancer cells and tissues, while the microRNA miR-582-3p is reduced. Circ_0000285 competitively binds miR-582-3p, freeing CCNB2 to rise. When circ_0000285 expression is inhibited, liver cancer cells undergo apoptosis, and their proliferation, migration and in vivo tumor growth are suppressed. Through this miR-582-3p/CCNB2 signaling axis, circ_0000285 promotes the malignant phenotype of hepatocellular carcinoma. A similar sponge arrangement operates in neuroblastoma, where circ_0000285 also interacts with miR-582-3p to promote CCNB2 expression, and in gastric cancer and nasopharyngeal carcinoma, where it binds miR-1278 to enhance the expression of FN1 and FNDC3B, genes involved in proliferation, migration and tumorigenic ability.
The molecular consequences extend beyond the microRNA axes. The review reports that inhibiting circ_0000285 in liver cancer, nasopharyngeal carcinoma, thyroid cancer, glioma, cervical cancer and neuroblastoma cells raises the protein expression of Bax or FUS while lowering Bcl-2, a shift in the balance of pro-death and pro-survival proteins that favors apoptosis. In cervical cancer cells, inhibition suppresses PCNA, cyclin D1 and BCL2 proteins while promoting LC3II/I or FUS expression, affecting cell growth through both proliferation and cell-death pathways. The authors additionally note that circ_0000285 enhances Wnt/beta-catenin signaling activity to promote neuroblastoma development, tying the circular RNA to one of the most consequential developmental pathways hijacked by tumors.
Clinically, the expression levels appear to carry prognostic and diagnostic weight, though with a twist that mirrors the expression split. In bladder cancer, where the RNA is downregulated, a decrease in circ_0000285 levels correlates positively with shorter overall survival, tumor size, tumor differentiation, lymph node metastasis, distant metastasis and TNM stage. In nasopharyngeal cancer, where the RNA is upregulated, the relationship inverts: an increase in circ_0000285 levels correlates negatively with shorter overall survival, tumor size, tumor differentiation, lymph node metastasis, distant metastasis, TNM stage and radiotherapy sensitivity. In cervical cancer, high expression levels are significantly correlated with tumor size, tumor differentiation, FIGO stage, CA125, SCC-Ag, HPV positivity and diagnosis, and in neuroblastoma they are significantly associated with INSS stage and amplification.
The authors address the bladder cancer contradiction directly. They suggest that such context-dependent heterogeneity holds considerable biological significance in non-coding RNA research and is likely driven by tissue-specific transcriptional and post-transcriptional regulation. The biogenesis of circular RNAs, including circ_0000285, depends on the transcription of their parental genes and the efficiency of back-splicing, a process controlled by tissue- or cell-type-specific splicing factors, RNA-binding proteins and the epigenetic landscape of regulatory elements. They also raise a more prosaic possibility: the low expression observed in bladder cancer could be an artifact of limited sample size rather than a true biological phenomenon, and they call for larger sample validation and further mechanistic studies in vitro and in vivo to clarify the reasons for the differential expression.
Translation into clinical practice remains distant. The review stresses that the tissue-specific expression profile, downregulated in bladder cancer but upregulated in other cancers, would demand a highly selective delivery system to minimize off-target effects and potential adverse events, and the authors point toward the design of nanocarriers capable of exploiting the unique tumor microenvironment of bladder cancer for precise targeting and regulation. They add that systematic evaluation of long-term safety in robust preclinical models will be essential before any clinical application. For now, the review’s contribution is a consolidated map: one stable circular RNA, a defined set of microRNA partners, a recurring cast of target genes, and a consistent association with aggressive disease across most of the cancers in which it has been measured.
Subject of Research: The roles and pathways of the circular RNA Hsa_circ_0000285 in cancer growth, metastasis and prognosis
Article Title: The roles and pathways of Hsa_circ_0000285 in cancer: a potential target for cancer therapy
Article References: Lv, Y., Li, D., Zhang, Q.-X., Zeng, T., Luo, X.-Y., Guo, Q., & Ren, Q.-Y. (2026). The roles and pathways of Hsa_circ_0000285 in cancer: a potential target for cancer therapy. Cell Division, 21(1), Article 7. https://doi.org/10.1186/s13008-026-00180-6
Image Credits: AI Generated
DOI: 10.1186/s13008-026-00180-6
Keywords: circular RNA, circ_0000285, non-coding RNA, miRNA sponge, cancer metastasis, hepatocellular carcinoma, gastric cancer, bladder cancer, prognosis, Wnt/beta-catenin, tumor biology, review
News Source: Nathaniel Bowman. (October 30, 2026). Circular RNA Hsa_circ_0000285 Emerges as a Cancer Growth Driver and Therapy Target. Scienmag.
