LncRNA LINC00662 Exerts an Oncogenic Effect on Osteosarcoma by the miR-16-5p/ITPR1 Axis

Abstract

Background. Osteosarcoma (OS) is one of the most malignant bone tumors and has a high metastatic rate. Increasing research has demonstrated the vital roles of long noncoding RNAs (lncRNAs) in human cancers, including OS. LncRNA LINC00662 has been revealed to act as an oncogene involved in multiple tumor progression. This study aimed to investigate the expression pattern, function, and regulatory mechanism of LINC00662 in OS. Methods. Patients who underwent OS surgery were involved in this study. Experiments including RT-qPCR, MTT, western blot, FISH, RNA pull-down, luciferase reporter, colony formation, transwell invasion and migration, and sphere formation assay were performed to investigate the regulatory role of LINC00662 in OS. Results. In the present study, our findings demonstrated the upregulation of LINC00662 expression in OS tissues and cells, and high expression of LINC00662 predicted a poor clinical prognosis of patients’ iNOS. Through a series of in vivo assays, LINC00662 knockdown suppressed OS cell proliferation, invasion, migration, and stemness property maintenance. Further mechanistical investigations indicated that LINC00662 functioned as a competing endogenous RNA (ceRNA) for sponging microRNA-16-5p (miR-16-5p) to upregulate the expression of IP receptor type 1 (ITPR1) in OS cells. Restoration assays validated the involvement of ITPR1 in LINC00662-mediated regulation of cell functions in OS. Conclusion. LINC00662 exerts oncogenic functions in OS by targeting the miR-16-5p/ITPR1 axis.

A pan-cancer analysis of the prognostic value of long non-coding RNA LINC00662 in human cancers

“…The remaining 32 studies were then carefully reviewed by reading the full article. Of them, 9 were eliminated due to the lack of eligible data, 9 were eliminated since they were physical experimental studies, and 14 studies ( Gong et al, 2018 ; Li et al, 2019 ; Wang et al, 2019 ; Cheng B. et al, 2020 ; Cheng L. et al, 2020 ; Guo et al, 2020 ; Liu and Meng, 2020 ; Tian et al, 2020 ; Wei et al, 2020 ; Zhang et al, 2020 ; Ma et al, 2021 ; Wu et al, 2021 ; Yu et al, 2021 ; Wang et al, 2022 ) were finally included for meta-analysis. The study screening procedure is presented in Figure 1 .…”

“…All of these articles were conducted in China and published between 2018 and 2022. The above articles included ten tumors, including three cases of OSA ( Liu and Meng, 2020 ; Yu et al, 2021 ; Wang et al, 2022 ), two cases of HCC ( Guo et al, 2020 ; Tian et al, 2020 ), two cases of CRC ( Wang et al, 2019 ; Cheng B. et al, 2020 ), one case of bladder cancer ( Ma et al, 2021 ), one case of lung cancer ( Gong et al, 2018 ), one case of CC ( Wei et al, 2020 ), one case of ESCC ( Zhang et al, 2020 ), one case of BC ( Cheng L. et al, 2020 ), one case of PCa ( Li et al, 2019 ), and one case of OC ( Wu et al, 2021 ). Nine of these articles ( Gong et al, 2018 ; Li et al, 2019 ; Wang et al, 2019 ; Cheng B. et al, 2020 ; Guo et al, 2020 ; Tian et al, 2020 ; Ma et al, 2021 ; Wu et al, 2021 ; Yu et al, 2021 ) reported OS, two ( Guo et al, 2020 ; Tian et al, 2020 ) reported RFS, and all studies reported clinical parameters.…”

“…Moreover, LINC00662 could be engaged in tumor proliferation, apoptosis, invasion and migration ( Cheng B. et al, 2020 ; Liu and Meng, 2020 ; Xu et al, 2021 ). Some studies have confirmed the critical link between LINC00662 and tumor-related signaling pathways ( Liu Y. L. et al, 2021 ; Yu et al, 2021 ). Taken together, LINC00662 could be a prospective prognostic marker and therapeutic target for most human malignancies.…”

“…In total, 14 articles (Gong et al, 2018;Li et al, 2019;Wang et al, 2019;Cheng B. et al, 2020;Guo et al, 2020;Liu and Meng, 2020;Tian et al, 2020;Wei et al, 2020;Zhang et al, 2020;Ma et al, 2021;Wu et al, 2021;Yu et al, 2021;Wang et al, 2022) presented usable data regarding the link between LINC00662 expression levels and Frontiers in Genetics frontiersin.org 0.71-3.33, p = 0.280) were not statistically significant. The results were presented in Figure 4 and Table 3.…”

“…Aberrant LINC00662 expression was first reported in lung tissues and cells ( Gong et al, 2018 ). Many recent studies have found that LINC00662 is overexpressed in numerous tumors, and this overexpression implies poor prognosis, such as prostate cancer (PCa) ( Li et al, 2019 ), colorectal cancer (CRC) ( Wang et al, 2019 ; Cheng B. et al, 2020 ), bladder cancer ( Ma et al, 2021 ), osteosarcoma (OSA) ( Yu et al, 2021 ), hepatocellular carcinoma (HCC) ( Guo et al, 2020 ; Tian et al, 2020 ), ovarian cancer (OC) ( Wu et al, 2021 ), cervical cancer (CC) ( Wei et al, 2020 ), glioma ( Geng et al, 2020 ; Wu et al, 2020 ), and gastric cancer (GC) ( Liu et al, 2018 ). Furthermore, elevated LINC00662 expression is usually linked to advanced clinicopathological features.…”