Evidence map›Paper›PMID 38689348›Full record

ArticleJournal of experimental & clinical cancer research : CR2024

LOXL1-AS1 contributes to metastasis in sonic-hedgehog medulloblastoma by promoting cancer stem-like phenotypes.

Anh Duy Do, Kuo-Sheng Wu, Shing-Shung Chu, Le Hien Giang, Yu-Ling Lin, Che-Chang Chang, Tai-Tong Wong, Chia-Ling Hsieh, Shian-Ying Sung

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Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Anh Duy DoInternational Ph.D. Program for Translational Science, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan.
Kuo-Sheng WuGraduate Institute of Clinical Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
Shing-Shung ChuGraduate Institute of Clinical Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
Le Hien GiangInternational Ph.D. Program for Translational Science, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan.
Yu-Ling LinAgricultural Biotechnology Research Center, Academia Sinica, Taipei, 11529, Taiwan.
Che-Chang ChangInternational Ph.D. Program for Translational Science, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan.
Tai-Tong WongGraduate Institute of Clinical Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
Chia-Ling HsiehThe Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan. chsieh2@dcb.org.tw.
Shian-Ying SungInternational Ph.D. Program for Translational Science, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan. ssung@tmu.edu.tw.ORCID http://orcid.org/0000-0002-0078-3899

Funding

Ministry of Science and Technology, Taiwan MOST 110-2314-B-038-137-MY3Ministry of Science and Technology, Taiwan MOST 111-2314-B-038-078-MY3Ministry of Science and Technology, Taiwan MOST 112-2314-B-001-007Ministry of Science and Technology, Taiwan NSTC 112-2314-B-169-001
6 · The paper itself

Abstract

backgroundMedulloblastomas (MBs) are one of the most common malignant brain tumor types in children. MB prognosis, despite improvement in recent years, still depends on clinical and biological risk factors. Metastasis is the leading cause of MB-related deaths, which highlights an unmet need for risk stratification and targeted therapy to improve clinical outcomes. Among the four molecular subgroups, sonic-hedgehog (SHH)-MB harbors clinical and genetic heterogeneity with a subset of high-risk cases. Recently, long non-coding (lnc)RNAs were implied to contribute to cancer malignant progression, but their role in MB remains unclear. This study aimed to identify pro-malignant lncRNAs that have prognostic and therapeutic significance in SHH-MB.

methodsThe Daoy SHH-MB cell line was engineered for ectopic expression of MYCN, a genetic signature of SHH-MB. MYCN-associated lncRNA genes were identified using RNA-sequencing data and were validated in SHH-MB cell lines, MB tissue samples, and patient cohort datasets. SHH-MB cells with genetic manipulation of the candidate lncRNA were evaluated for metastatic phenotypes in vitro, including cell migration, invasion, sphere formation, and expressions of stemness markers. An orthotopic xenograft mouse model was used to evaluate metastasis occurrence and survival. Finally, bioinformatic screening and in vitro assays were performed to explore downstream mechanisms.

resultsElevated lncRNA LOXL1-AS1 expression was identified in MYCN-expressing Daoy cells and MYCN-amplified SHH-MB tumors, and was significantly associated with lower survival in SHH-MB patients. Functionally, LOXL1-AS1 promoted SHH-MB cell migration and cancer stemness in vitro. In mice, MYCN-expressing Daoy cells exhibited a high metastatic rate and adverse effects on survival, both of which were suppressed under LOLX1-AS1 perturbation. Integrative bioinformatic analyses revealed associations of LOXL1-AS1 with processes of cancer stemness, cell differentiation, and the epithelial-mesenchymal transition. LOXL1-AS1 positively regulated the expression of transforming growth factor (TGF)-β2. Knockdown of TGF-β2 in SHH-MB cells significantly abrogated their LOXL1-AS1-mediated prometastatic functions.

conclusionsThis study proved the functional significance of LOXL1-AS1 in SHH-MB metastasis by its promotion of TGF-β2-mediated cancer stem-like phenotypes, providing both prognostic and therapeutic potentials for targeting SHH-MB metastasis.

Indexed as

Hedgehog ProteinsMedulloblastomaNeoplastic Stem CellsAnimalsCell Line, TumorCell MovementCerebellar NeoplasmsFemaleHumansMaleMiceNeoplasm MetastasisPhenotypePrognosisRNA, Long NoncodingHedgehog ProteinsRNA, Long NoncodingSHH protein, humanCancer stemnessLong non-coding RNALOXL1-AS1MedulloblastomaMetastasisTGF-β2

Identifiers

PMID38689348
PMCPMC11059759

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.