Deep RNA sequencing reveals the dynamic regulation of miRNA, lncRNAs, and mRNAs in osteosarcoma tumorigenesis and pulmonary metastasis

Abstract

Osteosarcoma (OS) is the most common pediatric malignant bone tumor, and occurrence of pulmonary metastasis generally causes a rapid and fatal outcome. Here we aimed to provide clues for exploring the mechanism of tumorigenesis and pulmonary metastasis for OS by comprehensive analysis of microRNA (miRNA), long non-coding RNA (lncRNA), and mRNA expression in primary OS and OS pulmonary metastasis. In this study, deep sequencing with samples from primary OS (n = 3), pulmonary metastatic OS (n = 3), and normal controls (n = 3) was conducted and differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs), and mRNAs (DEmRNAs) between primary OS and normal controls as well as pulmonary metastatic and primary OS were identified. A total of 65 DEmiRNAs, 233 DElncRNAs, and 1405 DEmRNAs were obtained between primary OS and normal controls; 48 DEmiRNAs, 50 DElncRNAs, and 307 DEmRNAs were obtained between pulmonary metastatic and primary OS. Then, the target DEmRNAs and DElncRNAs regulated by the same DEmiRNAs were searched and the OS tumorigenesis-related and OS pulmonary metastasis-related competing endogenous RNA (ceRNA) networks were constructed, respectively. Based on these ceRNA networks and Venn diagram analysis, we obtained 3 DEmiRNAs, 15 DElncRNAs, and 100 DEmRNAs, and eight target pairs including miR-223-5p/(CLSTN2, AC009951.1, LINC01705, AC090673.1), miR-378b/(ALX4, IGSF3, SULF1), and miR-323b-3p/TGFBR3 were involved in both tumorigenesis and pulmonary metastasis of OS. The TGF-β superfamily co-receptor TGFBR3, which is regulated by miR-323b-3p, acts as a tumor suppressor in OS tumorigenesis and acts as a tumor promoter in pulmonary metastatic OS via activation of the epithelial–mesenchymal transition (EMT) program.In conclusion, the OS transcriptome (miRNA, lncRNA, and mRNA) is dynamically regulated. These analyses might provide new clues to uncover the molecular mechanisms and signaling networks that contribute to OS progression, toward patient-tailored and novel-targeted treatments.

Long noncoding RNA MAPKAPK5‐AS1 promotes colorectal cancer proliferation by partly silencing p21 expression

“…In recent years, more and more tumor‐associated lncRNAs have been discovered . A large number of published works have reported that these lncRNAs play an important role in multiple tumors . Our previous research shows that lncRNA SNHG17 can promote the proliferation of CRC cells by inhibiting the expression of p57 .…”

“…18 A large number of published works have reported that these lncRNAs play an important role in multiple tumors. [19][20][21][22][23] Our previous research shows that lncRNA SNHG17…”

WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m6A-dependent manner

“…Osteosarcoma is a primary malignant bone tumor that is common among childhood and adolescents worldwide 1 . Despite the improvements including multi-agent chemotherapy with surgery in recent years, the 5-year survival rate is~70% for localized osteosarcoma and is~30% for recurrent and metastatic osteosarcoma 2,3 . Therefore, a better understanding of molecular mechanism is urgent for developing novel therapeutic strategies for osteosarcoma.…”

Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma

“…DLX2 was indicated to increase the risk of metastasis in prostate cancer patients with a high expression of Ki67 (27). In addition, CLSTN2 was demonstrated to be involved in both the tumorigenesis and pulmonary metastasis of osteosarcoma (28). Interestingly, REG3A was found to promote cell proliferation in gastric and colorectal cancers (29,30).…”