scholarly journals LOXL1-AS1 predicts poor prognosis and promotes cell proliferation, migration, and invasion in osteosarcoma

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Si Chen ◽  
Weiguo Li ◽  
Ai Guo

Abstract lncRNA LOXL1 antisense RNA 1 (lncRNA LOXL1-AS1) was recently found to function as oncogenic lncRNA in glioblastoma, prostate cancer, and medulloblastoma. The role of LOXL1-AS1 in osteosarcoma was still unknown. In our study, we found LOXL1-AS1 expression levels were higher in osteosarcoma tissues and cell lines than normal bone tissues and normal osteoblast cell line, respectively. Moreover, high-expression of LOXL1-AS1 was correlated with Enneking stage, tumor size, distant metastasis, histological grade, and overall survival time in osteosarcoma patients. Furthermore, LOXL1-AS1 overexpression acted as an independent poor predictor for overall survival in osteosarcoma patients. The loss-of-function studies showed knockdown of LOXL1-AS1 dramatically inhibited osteosarcoma cell proliferation, migration, and invasion through suppressing PI3K-AKT pathway. In conclusion, LOXL1-AS1 predicts clinical progression and poor prognosis in osteosarcoma patients and functions as oncogenic lncRNA to regulate cell proliferation, cell cycle, migration, and invasion.

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Qiang Huang ◽  
Shu-yan Shi ◽  
Hai-bo Ji ◽  
Shu-xing Xing

Abstract Aim: In previous studies, numerous dysregulated long non-coding RNAs (lncRNAs) were identified by RNA-sequencing (RNA-seq). However, the relationship between lncRNA and osteosarcoma remains unclear. In the present study, the function and mechanism of lncRNA BE503655 were investigated. Methods: Transwell, cell cycle and proliferation were used to evaluate the function of lncRNA BE503655. Real-time PCR and Western blotting were used to detect the expression of lncRNA BE503655 and β-catenin. Results: LncRNA BE503655 is overexpressed in human osteosarcoma and osteosarcoma cell lines. Knockdown lncRNA BE503655 suppresses cell proliferation, invasion and migration. High expression of BE503655 was significantly related to Enneking stage, distant metastasis and histological grade. Moreover, we also provided evidences that lncRNA BE503655 played its functions dependent on regulation of Wnt/β-catenin signaling in osteosarcoma. Conclusion: Taken together, we verified the role of lncRNA BE503655 and provided possible mechanism in osteosarcoma. Our study provided new insights into clinical treatment of osteosarcoma and further intervention target.


2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Weidong He ◽  
Ming Lu ◽  
Dongbo Xiao

AbstractThe dysregulated expression of LSINCT5 (long stress-induced non-coding transcript 5) has been found in various human tumors, and was generally related to cancer progression and unfavorable prognosis. Although the role of LSINCT5 in osteosarcoma was reported not long ago, the sample size of that study was limited. Our study presented more evidence about the clinical significance and biological function of LSINCT5 in osteosarcoma. In our results, we found LSINCT5 expression was increased in osteosarcoma tissue samples and cell lines, and high LSINCT5 expression was associated with advanced Enneking stage, large tumor size, high histological grade and present distant metastasis. Meanwhile, we observed high LSINCT5 expression was correlated with worse overall survival, and high LSINCT5 expression could be an independent poor predictor for overall survival in osteosarcoma cases. Moreover, we found inhibition of LSINCT5 expression suppressed cell proliferation, migration and invasion in vitro, and LSINCT5 overexpression dramatically facilitated cell proliferation, migration and invasion in vitro. In conclusion, our study suggests that LSINCT5 exerts oncogenic function in osteosarcoma cells, and may be a potential predictor for clinical outcome in osteosarcoma patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Ying Jiang ◽  
Chunlei Zhou ◽  
Qiang Gao ◽  
Zhi-Qi Yin ◽  
Jingwen Wang ◽  
...  

Aberrant expression of FAM64A was correlated with cell proliferation in various cancer types. We examined the expression of FAM64A and the upstream gene miR-493 in OS. The functions of miR-493 were revealed through extensive experiments. We found an increase of FAM64A gene and protein in OS tissues. Overexpression of FAM64A resulted in promoting tumor proliferation, migration, and invasion. The miR-493 targeted and negatively regulated FAM64A. Our data showed that upregulation of FAM64A in OS correlated with poor prognosis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuhong Dai ◽  
Ning Li ◽  
Ming Zhou ◽  
Yue Yuan ◽  
Ding Yue ◽  
...  

AbstractThe treatment of patients with advanced-stage osteosarcoma represents a major challenge, with very few treatments currently approved. Although accumulating evidence has demonstrated the importance of lncRNAs in osteosarcoma, the current knowledge on the functional roles and molecular mechanisms of lncRNA endogenous born avirus-like nucleoprotein (EBLN3P) is limited. At present, the expressions of EBLN3P and miR-224-5p in osteosarcoma tissues were quantified by reverse transcription-quantitative PCR assay, and the expression of Ras-related protein 10 (Rab10) in osteosarcoma tissues was quantified by immunohistochemistry and western-blotting. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of EBLN3P, Rab10 and miR-224-5p. The regulatory role of EBLN3P or miR-224-5p on cell proliferation, migration and invasion ability were verified by Cell Counting Kit-8, wound healing and Transwell assays, respectively. The interaction among EBLN3P, miR-224-5p and Rab10 were testified by luciferase. The increased expression of EBLN3P and Rab10 and decreased expression of miR-224-5p were observed in osteosarcoma tissues and cell lines. Besides, the overexpression of EBLN3P or knockdown of miR-224-5p were revealed to promote the proliferation, migration and invasion of osteosarcoma cells. Bioinformatics analysis and luciferase assay revealed that EBLN3P could directly interacted with miR-224-5p to attenuate miR-224-5p binding to the Rab10 3′-untranslated region. Furthermore, the mechanistic investigations revealed activation of the miR-224-5p/Rab10 regulatory loop by knockdown of miR‐372-3p or overexpression of Rab10, thereby confirming the in vitro role of EBLN3P in promoting osteosarcoma cell proliferation, migration and invasion. To the best of our knowledge, the present study is the first to demonstrate that EBLN3P may act as a competitive endogenous RNA to modulate Rab10 expression by competitive sponging to miR-224-5p, leading to the regulation of osteosarcoma progression, which indicates a possible new approach to osteosarcoma diagnosis and treatment.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Biyong Deng ◽  
Runsang Pan ◽  
Xin Ou ◽  
Taizhe Wang ◽  
Weiguo Wang ◽  
...  

Purpose. Osteosarcoma (Os) is the most frequent malignant tumor of the bone in the pediatric age group, and accumulating evidences show that lncRNAs play a key role in the development of Os. Thus, we investigated the role of RBM5-AS1 and its molecular mechanism. Methods. The expression of RBM5-AS1 in Os tissues and cell lines was detected by real-time polymerase chain reaction (QPCR). The effect of RBM5-AS1 on the proliferation of Os cells was detected using CCK8 assays and flow cytometry. The effect of RBM5-AS1 on the migration and invasion of Os cells was detected by transwell assays. And we performed QPCR and western blotting assays to investigate the relationship between RBM5-AS1 and RBM5. Finally, western blotting assays were performed to explore the mechanism of RBM5. Results. LncRNA RBM5-AS1 was overexpressed in the Os tissues and cell lines. And lncRNA RBM5-AS1 promoted Os cell proliferation, migration, and invasion in vitro and tumor growth in vivo. LncRNA RBM5-AS1 targets RBM5 in Os cells. Conclusion. To sum up, the results showed that lncRNA RBM5-AS1 promotes cell proliferation, migration, and invasion in Os.


2020 ◽  
Author(s):  
Ning Wang ◽  
Qin-Xue Cao ◽  
Jun Tian ◽  
Lu Ren ◽  
Hai-Ling Cheng ◽  
...  

Abstract Background Ovarian cancer remains one of the most challenging areas of cancer research. Recent studies have shown that many long non-coding RNAs (lncRNAs) are abnormally expressed in ovarian cancer and involved in the pathological progress of ovarian cancer. In the present study, we aimed to investigate the role of lncRNA LINC00858 and the potential mechanism in ovarian cancer. Methods The qRT-PCR was used to measure the expression levels of LINC00858 and miR-134-5p in ovarian cancer tissue specimens and cell lines. Loss-of-function assays were performed to investigate the role of LINC00858 in ovarian cancer progression. MTT assay was carried out to measure cell proliferation. Transwell assays were performed to determine the migration and invasion of ovarian cancer cells. Biological information analysis and luciferase report gene assay were used to verify potential downstream genes of LINC00858. The xenograft mouse model was established to analyze tumor growth in vivo. Results Our results showed that LINC00858 was highly expressed in human ovarian cancer tissue specimens and cell lines. Loss-of-function assays showed that knockdown of LINC00858 significantly inhibited cell proliferation, migration and invasion of SKOV3 cells, and suppressed tumor growth in mouse xenograft models. Mechanistic studies revealed that LINC00858 acted as a sponge of miR-134-5p and then regulated the expression TRIM44 in SKOV3 cells. Furthermore, rescue experiments illustrated that inhibition of miR-134-5p restored the inhibitory effects of LINC00858 knockdown on ovarian cancer cell proliferation, migration and invasion. TRIM44 overexpression could counteract the inhibitory effects of miR-134-5p mimics on ovarian cancer cells. Conclusion In conclusion, these findings demonstrated that LINC00858 exerted oncogenic role in ovarian cancer, which was mediated by miR-134-5p/TRIM44 axis. Thus, LINC00858 might be a therapeutic target for the treatment of ovarian cancer.


2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Shian Liao ◽  
Sijia Zhou ◽  
Chao Wang

Gastric adenocarcinoma predictive long intergenic non-coding (GAPLINC) is a novel long non-coding RNA (lncRNA) and has been found to function as an oncogenic lncRNA in gastric cancer, colorectal cancer, and bladder cancer. The expression status and biological function of GAPLINC in osteosarcoma are still unknown. Thus, we analyzed the association between GAPLINC expression and clinicopathological characteristics in osteosarcoma clinical samples, and conducted loss-of-function study in osteosarcoma cell lines. In our results, GAPLINC expression is elevated in osteosarcoma tissues and cell lines, and correlated with advanced Enneking stage, present distant metastasis, and poor histological grade. Survival analyses indicated that GAPLINC expression was negatively associated with overall survival, and GAPLINC high-expression was an independent risk factor in osteosarcoma patients. The in vitro studies showed knockdown of GAPLINC depressed osteosarcoma cell migration and invasion via inhibiting CD44 expression, but no effect on cell proliferation. In conclusion, GAPLINC may serve as a potential biomarker for predicting prognosis and developing therapy for osteosarcoma.


Author(s):  
Yu Wang ◽  
Hui Leng ◽  
Hui Chen ◽  
Lei Wang ◽  
Nan Jiang ◽  
...  

Ubiquitin-conjugating enzyme E2T (UBE2T), a member of the E2 family, was found to be overexpressed in a great many cancers such as bladder cancer, lung cancer, and prostate cancer. However, there have been no reports on the role of UBE2T in osteosarcoma. In this study, we tried to make the effects of UBE2T on osteosarcoma clear. The study results showed that UBE2T was overexpressed in osteosarcoma tissues and cell lines. Moreover, UBE2T knockdown inhibited osteosarcoma cell proliferation, migration, and invasion. We also observed that UBE2T downregulation could suppress the activity of the PI3K/Akt signaling pathway. Therefore, we concluded that UBE2T exerted its inhibitory effects on osteosarcoma cells via suppressing the PI3K/Akt signaling pathway. These findings indicated that UBE2T may be a potential therapeutic target for osteosarcoma treatment.


2016 ◽  
Vol 15 (6) ◽  
pp. NP105-NP112 ◽  
Author(s):  
Fei Wang ◽  
Dapeng Yu ◽  
Zhen Liu ◽  
Ruijie Wang ◽  
Yan Xu ◽  
...  

MicroRNAs are highly conserved noncoding RNA that negatively modulate protein expression at a posttranscriptional and/or translational level and are deeply involved in the pathogenesis of several types of cancers. To date, the potential microRNAs regulating the growth and progression of osteosarcoma are not fully identified yet. Previous reports have shown differentially expressed miR-125b in osteosarcoma. However, the role of miR-125b in human osteosarcoma has not been totally illuminated. In this study, we have shown that miR-125b was downregulated in human osteosarcoma tissues compared to the adjacent tissues and effects as a tumor suppressor in vitro. We found that stable overexpression of miR-125b in osteosarcoma cell lines U2OS and MG-63 inhibited cell proliferation, migration, and invasion. Our data also verified that Bcl-2 is the target of miR-125b. Meanwhile, we showed that Bcl-2 was inversely correlated with miR-125b in osteosarcoma tissues. More importantly, we proved that miR-125b increased the chemosensitivity of osteosarcoma cell lines to cisplatin by targeting Bcl-2. In conclusion, our data demonstrate that miR-125b is a tumor suppressor and support its potential application for the treatment of osteosarcoma in the future.


2018 ◽  
Vol 13 (1) ◽  
pp. 396-403 ◽  
Author(s):  
Yao-Ping Yu ◽  
Jian-Guo He ◽  
Ping Li ◽  
Ning-Hui Qiu ◽  
Li-Jun Wang ◽  
...  

AbstractObjectiveThis study is aimed at exploring the role of TUFT1 in osteosarcomas.MethodsWe investigated the expression of TUFT1 in osteosarcoma cell lines and explored the correlation between TUFT1 expression and prognosis in osteosarcoma patients based on the expression data downloaded from Gene Expression Omnibus (GEO) website. The effects of TUFT1 on osteosarcoma cell proliferation, migration and invasion were investigated by silencing TUFT1 in osteosarcoma MG63 cell line. Finally, western blot was performed to determine the expression changes of MAPK signaling pathway related proteins after silencing TUFT1.ResultsWe found that the expression of TUFT1 was significantly up-regulated in osteosarcoma cell lines compared with the normal control. Using Kaplan-Meier analysis, we identified that high TUFT1 expression was positively correlated with poor prognosis in osteosarcoma patients. Furthermore, knockdown of TUFT1 remarkably inhibited MG63 cell proliferation, migration and invasion. Using western blot analysis, we found that the phosphorylation levels of MEK and ERK were reduced obviously in MG63 cells after silencing TUFT1 (p<0.01).ConclusionsOur results demonstrated that TUFT1 plays a promoting role in MG63 cell proliferation and metastasis and has the potential to be a predictor as well as a therapeutic target for osteosarcoma patients.


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