Long noncoding RNA MANCR drives glioblastoma growth via miR-205-5p and CASP3

A new study published in Cancer Cell International points to a long noncoding RNA called MANCR, the Mitotically Associated Non-Coding RNA, as a potential driver of the disease. The researchers report that MANCR is elevated in glioblastoma tissues and cell lines, that higher levels correlate with poorer patient survival, and that the molecule appears to fuel tumor progression through a specific regulatory pathway involving the microRNA miR-205-5p and the apoptosis-related protein caspase 3.

Long noncoding RNAs are RNA molecules longer than 200 nucleotides that do not code for proteins, but many have emerged as important regulators of cancer biology. To probe MANCR’s role, the team first assessed its expression levels using publicly available datasets and then validated the findings in glioblastoma cell lines. They found MANCR consistently elevated in tumor samples and cells, and survival analysis linked high MANCR expression to reduced overall survival, suggesting the molecule could serve as a prognostic biomarker.

The researchers then ran a series of functional assays to test what MANCR actually does inside glioblastoma cells. When they silenced MANCR, cell proliferation, invasion, and colony formation all dropped, while apoptosis increased. Flow cytometric analysis using Annexin V/PI staining showed a larger population of apoptotic cells after MANCR knockdown, and western blotting confirmed the effect through increased levels of cleaved caspase 3, a hallmark of programmed cell death. In other words, removing MANCR appeared to lift a brake on the cellular self-destruct machinery that glioblastoma cells normally keep suppressed.

The mechanistic core of the study lies in what the authors describe as a sponging relationship. MANCR appears to bind and sequester miR-205-5p, a microRNA that would otherwise restrain caspase 3. With MANCR soaking up miR-205-5p, caspase 3 regulation shifts in a way that favors tumor cell survival and spread. RNA immunoprecipitation experiments supported this interaction, and rescue experiments strengthened the case: when the researchers inhibited miR-205-5p, they partially reversed the effects of MANCR knockdown on glioblastoma cells, indicating that the microRNA sits downstream of MANCR in the pathway.

Taken together, the findings sketch an oncogenic circuit in which MANCR promotes proliferation and invasion while suppressing apoptosis through the miR-205-5p/CASP3 axis. The authors suggest this network could represent both a potential therapeutic target and a promising biomarker for glioblastoma. However, they are careful to note the limits of the current work. The evidence comes from public datasets, cell line experiments, and in vitro functional assays, and the study has not yet been confirmed in animal models or clinical settings. The researchers state that further in vivo and clinical validation is warranted before the MANCR/miR-205-5p/CASP3 axis can be considered a validated target. The article was published open access on 27 October 2026 as a peer-reviewed, accepted manuscript shared early for faster access, with a final version of record to follow.

Subject of Research: The role of the long noncoding RNA MANCR in glioblastoma progression via the miR-205-5p/CASP3 axis

Article Title: Elevated MANCR expression promotes glioblastoma progression through miR-205-5p sponging and CASP3 regulation

Article References: Yadav, B., Patel, B., Kansara, S., Sharma, R. D., Pandey, V., & Pandey, A. K. (2026). Elevated MANCR expression promotes glioblastoma progression through miR-205-5p sponging and CASP3 regulation. Cancer Cell International. https://doi.org/10.1186/s12935-026-04485-y

Image Credits: AI Generated

DOI: 10.1186/s12935-026-04485-y

Keywords: glioblastoma, long noncoding RNA, MANCR, miR-205-5p, caspase 3, apoptosis, lncRNA, prognostic biomarker, cell invasion, sponging mechanism, Cancer Cell International, therapeutic target