Mislocalized cytoplasmic p27 activates PAK1‐mediated metastasis and is a prognostic factor in osteosarcoma

Chen, Xiang; Cates, Justin M.; Du, Yu; Jain, Antrix; Jung, Sung Yun; Li, Xiao Nan; Hicks, John; Man, Tsz Kwong

doi:10.1002/1878-0261.12624

Cited by 12 publications

(7 citation statements)

References 31 publications

(48 reference statements)

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“…Recently, an increasing number of diagnostic and prognostic biomarkers of osteosarcoma patients have been identified. For example, Chen et al [ 5 ] reported that tumor suppressor p27 is a novel biomarker for the metastasis and survival status in osteosarcoma patients. Moreover, Huang et al [ 6 ] discovered that dysregulated circRNAs serve as prognostic and diagnostic biomarkers in osteosarcoma patients, and the relative potential mechanism mainly attributes to the regulation of downstream signaling pathways by sponging microRNA.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of prognostic tumor microenvironment-related genes in osteosarcoma patients

Liu

Tian

et al. 2020

BMC Cancer

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Background Tumor microenvironment (TME) plays an important role in malignant tumors. Our study aimed to investigate the effect of the TME and related genes in osteosarcoma patients. Methods Gene expression profiles and clinical data of osteosarcoma patients were downloaded from the TARGET dataset. ESTIMATE algorithm was used to quantify the immune score. Then, the association between immune score and prognosis was studied. Afterward, a differential analysis was performed based on the high- and low-immune scores to determine TME-related genes. Additionally, Cox analyses were performed to construct two prognostic signatures for overall survival (OS) and disease-free survival (DFS), respectively. Two datasets obtained from the GEO database were used to validate signatures. Results Eighty-five patients were included in our research. The survival analysis indicated that patients with higher immune score have a favorable OS and DFS. Moreover, 769 genes were determined as TME-related genes. The unsupervised clustering analysis revealed two clusters were significantly related to immune score and T cells CD4 memory fraction. In addition, two signatures were generated based on three and two TME-related genes, respectively. Both two signatures can significantly divide patients into low- and high-risk groups and were validated in two GEO datasets. Afterward, the risk score and metastatic status were identified as independent prognostic factors for both OS and DFS and two nomograms were generated. The C-indexes of OS nomogram and DFS nomogram were 0.791 and 0.711, respectively. Conclusion TME was associated with the prognosis of osteosarcoma patients. Prognostic models based on TME-related genes can effectively predict OS and DFS of osteosarcoma patients.

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Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of prognostic tumor microenvironment-related genes in osteosarcoma patients

Liu

Tian

et al. 2020

BMC Cancer

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“…We speculated that the LINC00662/miR-30b-3p/ELK1 axis may be involved in the progression of osteosarcoma by regulating these signalling pathways. In addition, some potential downstream genes of miR-30b-3p, such as ATG5 [61], PAK1 [62], FOXP4 [63], and MYO10 [64] also exerted crucial roles in osteosarcoma. We speculated that these genes may be also involved in the regulatory mechanism of LINC00662/miR-30b-3p in osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of lncRNA LINC00662 suppresses malignant behaviour of osteosarcoma cells via competition with miR-30b-3p to regulate ELK1 expression

Wang

et al. 2022

J Orthop Surg Res

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Purpose Osteosarcoma is a type of bone malignancy that mainly occurred in teenagers. This investigation is aimed to clarify the effect of long non-coding RNA (lncRNA) LINC00662 on the proliferation, migration, and invasion in osteosarcoma and explore the underlying action mechanisms. Methods The mRNA expression of LINC00662 was determined by real-time quantitative polymerase chain reaction. Cell proliferation, migration, and invasion were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, and transwell assays, respectively. A dual-luciferase reporter assay was used to validate the target relationships Between microRNA (miR)-30b-3p and LINC00662/ ETS domain-containing protein 1 (ELK1). Western blotting was performed to determine the protein expression of ELK1. Xenograft model was established to evaluate the effects of LINC00662 silencing on tumor growth in vivo. Results LncRNA LINC00662 and ELK1 were significantly increased, while miR-30b-3p was reduced in osteosarcoma tissues. The results of functional experiments indicated that transfection of small hairpin (sh)-LINC00662 and miR-30b-3p mimics repressed the migration, invasion, and proliferation of osteosarcoma cells. LncRNA LINC00662 also appeared to sponge miR-30b-3p in order to affect the expression of ELK1. Simultaneously, there were weak negative correlations between the expression of miR-30b-3p and LINC00662/ELK1 in osteosarcoma tissues. Rescue experiments suggested that ELK1 overexpression and downregulation of miR-30b-3p reversed the suppressive effects of sh-LINC00662 on the cell migration, invasion, and proliferation in osteosarcoma. Conclusions The current study indicated that knockdown of LINC00662 repressed cell migration, invasion, and proliferation through sponging miR-30b-3p to regulate the expression of ELK1 in osteosarcoma. These results may uncover a promising target for the treatment of osteosarcoma.

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“…Fortunately, soft tissue deficiency after segmental mandibular resection was small because of the exophilic nature of the tumor. The presence of mislocalized cytoplasmic p27 is reported to be associated with higher metastatic status and poorer survival of osteosarcoma [17]. As clinical factors, proximal location of osteosarcoma in the long bone of an extremity portends a worse clinical outcome than tumors located in the distal long bones [18].…”

Section: Discussionmentioning

confidence: 99%

Osteosarcoma of the Mandible in an Elderly Patient

Hoshi

Abe

Onodera

et al. 2022

Case Reports in Dentistry

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Osteosarcoma is a malignant tumor in which the cancerous cells produce an osteoid matrix or mineralized bone. Jaw bones are affected in 6% of all osteosarcomas and are the fourth most common site of origin. Surgical treatment of osteosarcoma in elderly patients is rarely reported. Here, we report successful treatment of osteosarcoma arising in the mandible of a 90-year-old man. The patient was referred to our institution for diagnosis and treatment of an oral lesion. Intraoral examination revealed that a hard mass measuring 35 × 27 mm was located on the floor of the oral cavity, attached to the bone, and its growth displaced the tongue posteriorly. Therefore, he experienced difficulty in speech and swallowing. Biopsy of the mandibular mass was suspicious for chondrosarcoma. Preoperative examination did not detect critical risks for general anesthesia or surgery. Based on a clinical diagnosis of a malignant bone tumor of the mandible, segmental mandibular resection with reconstruction using a titanium plate was performed. Surgical site infection occurred on postoperative day 12, which was resolved by drainage, local irrigation, and administration of antibiotics. There was no delirium or cardiovascular or pulmonary complications. Surgery resolved the patient’s difficulties in speech and swallowing. There was no evidence of tumor recurrence or metastasis 4 years after surgery. This case showed that it was not necessary to exclude surgical treatment merely because the patient was 90 years old. Indications for surgery should be determined individually to improve the patient’s quality of life.

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Mislocalized cytoplasmic p27 activates PAK1‐mediated metastasis and is a prognostic factor in osteosarcoma

Cited by 12 publications

References 31 publications

Comprehensive analysis of prognostic tumor microenvironment-related genes in osteosarcoma patients

Comprehensive analysis of prognostic tumor microenvironment-related genes in osteosarcoma patients

Knockdown of lncRNA LINC00662 suppresses malignant behaviour of osteosarcoma cells via competition with miR-30b-3p to regulate ELK1 expression

Osteosarcoma of the Mandible in an Elderly Patient

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