LncRNA HULC induces the progression of osteosarcoma by regulating the miR-372-3p/HMGB1 signalling axis

Abstract

Background: Osteosarcoma is a malignancy that normally affects children, adolescents, and young adults. Although accumulating evidence has demonstrated the importance of HULC in osteosarcoma, little is reported about its functional roles and molecular mechanisms. Methods: The expression of HULC and miR-372-3p in osteosarcoma tissues was quantified by qRT-PCR. The regulatory roles of HULC and miR-372-3p on cell proliferation, apoptosis, migration and invasion were determined by CCK-8, colony formation, flow cytometry, wound healing, and transwell assays, respectively. The bioinformatics prediction software RAID v2.0 was used to predict the putative binding sites. The interactions among HULC, miR-372-3p and HMGB1 were explored by luciferase assay and western blot assay. Results: Our results revealed elevated HULC and decreased miR-372-3p expression in both osteosarcoma tissues and cell lines. Overexpression of HULC or knockdown of miR-372-3p promoted osteosarcoma cell proliferation, migration and invasion and induced cell apoptosis. Bioinformatics and luciferase assays verified that HULC directly interacted with miR-372-3p to attenuate miR-372-3p binding to the HMGB1 3′-UTR. Furthermore, mechanistic investigations confirmed that activation of the miR-372-3p/HMGB1 regulatory loop by knockdown of miR-372-3p or overexpression of HMGB1 reversed the in vitro roles of HULC in promoting osteosarcoma cell proliferation, migration and invasion. Conclusion: Our study is the first to demonstrate that HULC may act as a ceRNA to modulate HMGB1 expression by competitively sponging miR-372-3p, leading to the regulation of osteosarcoma progression, which provides new insight into osteosarcoma diagnosis and treatment.

Identifying modules of cooperating cancer drivers

“…= 71) and as part of the core RS. HULC is a long non‐coding RNA that has been identified as a driver of tumorigenesis in multiple cancers (Yu et al, 2017; Klec et al, 2019; Ghafouri‐Fard et al, 2020), including liver cancer, osteosarcoma, cervical cancer, pancreatic, stomach, and ovarian cancers (Panzitt et al, 2007; Zhang et al, 2016; Chen et al, 2017a; Wang et al, 2020; Li et al, 2020; Lu et al, 2020). HULC expression is a predictor of poor prognosis across multiple cancers (Peng et al, 2014; Jin et al, 2016; Fan et al, 2017; Chen et al, 2017b), and HULC silencing enhanced the effectiveness of chemotherapy in stomach cancer cell lines (Zhang et al, 2016).…”

Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells

“…We also observed that the administration of sublethal concentrations of piperine disrupted classical events related to TGF-β1 induced-EMT processes, such as morphology changes, phenotypic alterations, increased cell motility and expression of metalloproteinases [66,76]. In order to monitor the effect of piperine on cell motility, we initially used the wound assay, a widely used technique [55,[77][78][79]. The results showed that piperine abrogated the increased cell motility induced by TGF-β1.…”

Identifying Modules of Cooperating Cancer Drivers

“…= 71), and as part of the core RS. HULC is a long non-coding RNA that has been identified as a driver of tumorigenesis in multiple cancers [37,38,39], including liver cancer, osteosarcoma, cervical cancer, pancreatic, stomach and ovarian cancers [40,41,42,43,44,45]. HULC expression is a predictor of poor prognosis across multiple cancers [46,47,48,49], and HULC silencing enhanced the effectiveness of chemotherapy in stomach cancer cell lines [44].…”