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Tumor Discovery LncRNA HA117 in osteosarcoma regulation

osteosarcoma is rare, it is associated with a variety of of osteosarcoma cells by activating the PI3K/Akt pathway.
genetic abnormalities in humans. Unlike other tumors, Huang et al. reported that lncRNA MEG3 can enhance the
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5
a range of hazardous genetic and environmental factors chemosensitivity of osteosarcoma by regulating antitumor
can lead to the development of osteosarcoma, making it immunity through the has-miR-21-5p/p53 pathway and
defined by phenotype rather than by molecular markers. autophagy. Wang et al. discovered that lncRNA DANCR
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6,7
Osteosarcoma is a genetically heterogeneous and unstable can act as a competing endogenous RNA, influencing
tumor with a high incidence rate. It is prone to local the expression of ROCK1 by mediating has-miR-335-5p
recurrence, metastasis, and chemoresistance, leading to and has-miR-1972, thereby promoting the proliferation
a poor prognosis. 8-10 Despite significant improvements and metastasis of osteosarcoma. Yang et al. found that
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in the treatment of osteosarcoma in recent years, the lncRNA RP11-361F15.2 promotes the development of
prognosis for most patients with recurrent and metastatic osteosarcoma by inhibiting the M2-like polarization of
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osteosarcoma remains poor. Most existing studies have CPEB4-associated tumor macrophages.
shown that osteosarcoma is an aggressive cancer of the In our previous studies 25-27 , we investigated
skeletal system, with oncogenes and tumor suppressor chemotherapy drug resistance in the treatment of acute
genes potentially involved in the migration, angiogenesis, promyelocytic leukemia following the administration of all-
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apoptosis, and proliferation of tumor cells. Therefore, it is trans retinoic acid (ATRA). We induced ATRA resistance
necessary to combine the findings of molecular biology to in wild-type HL-60 cells using a low-dose, repeated, and
improve treatment and prognosis and to elucidate the basic increasing concentration approach, ultimately establishing
biology of osteosarcoma. the multidrug-resistant HL-60/ATRA cell model.
In recent decades, numerous osteosarcoma-related Subsequently, by analyzing the differentially expressed
molecular targets have been discovered or confirmed, genes (DEGs) between drug-resistant and wild-type
including miRNA, long noncoding RNA (lncRNA), mRNA, strains using gene chips, we discovered a new differentially
and various disease pathways. Recent studies have begun to expressed sequence and named it HA117. This sequence
understand osteosarcoma at the molecular level and have is located on the long arm of chromosome 14 in region
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identified new therapeutic targets. Previous studies have 14q24.2, between the RGS6 and DPF3 genes. Subsequent
found that about 95% of tumors have mutations in the p53 analysis confirmed that HA117 (GeneBank accession ID:
pathway, with TP53 mutations often being translocations CB214920) is a lncRNA with a length of 230 bp. Our further
or focal deletions. In addition, mutated genes, such as RB1, research has demonstrated that lncRNA HA117 plays an
ATRX, and DLG2, have been identified. 13,14 Studies have also important role in leukemia chemotherapy, suggesting its
found that some mature miRNAs, such as hsa-miR-206, involvement in chemotherapy drug resistance in leukemia.
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hsa-miR-195-5p, and has-miR-340-5p, are down-regulated An earlier study on the expression of lncRNA HA117 in
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in osteosarcoma and are associated with poor prognoses, four types of solid tumors confirmed that HA117, which is
while others, such as has-miR-17-5p, are up-regulated. 15-17 associated with multidrug resistance, is widely present in
In addition, recent studies have shown that lncRNAs play malignant tumor tissues. Its high expression may indicate
important roles in various aspects of cell biology and an increase in tumor resistance and poor prognosis,
may promote the occurrence and development of tumors although its specific mechanism of action remains unclear.
by regulating cell proliferation, apoptosis, metastasis, Despite reports on HA117’s role in drug resistance in
stemness, and therapeutic resistance. Therefore, lncRNAs various tumor cells or tumors, there have been no studies
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may serve as effective biomarkers for cancer diagnosis and on its application in osteosarcoma. Therefore, to determine
treatment or as therapeutic targets. However, up to now, whether HA117 can serve as a predictive indicator for
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only a small portion of lncRNAs and their functions have tumor resistance and prognosis, we further investigated its
been recognized in cancer research, and the functions of mechanism of action in osteosarcoma.
most lncRNAs remain unclear; therefore, more in-depth The purpose of this study was to accurately predict
studies of the functions of lncRNAs are needed. the target genes of HA117 in osteosarcoma using
As a “star molecule,” lncRNA has been reported to bioinformatics methods and to explore the functional
play key roles in the occurrence and development of mechanisms of these target genes. We performed
osteosarcoma. Sun et al. found that up-regulation of quantitative analysis on HA117 and other mRNAs using 51
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lncRNA HULC expression suggests poor prognosis in whole transcriptome samples downloaded from a public
osteogenic sarcoma and can significantly promote cell database. We combined two methods to predict the target
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metastasis of osteosarcoma. Dong et al. found that genes of HA117 and conducted Gene Ontology (GO) and
lncRNA MALAT1 promotes proliferation and metastasis Reactome pathway enrichment analysis on these target

Volume 3 Issue 3 (2024) 2 doi: 10.36922/td.3670