Oncogenic non-coding RNA NEAT1 promotes the prostate cancer cell growth through the SRC3/IGF1R/AKT pathway

Xiong, Wei; Huang, Chí; Deng, Huanghao; Jian, Chengzhu; Zen, Cong; Ye, Kun; Zhong, Zhaohui; Zhao, Xiaokun; Zhu, Liang

doi:10.1016/j.biocel.2017.12.005

Cited by 53 publications

(36 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The molecular heterogeneity of prostate cancer can make its early diagnosis and treatment problematic; thus, the identification of accurate molecular biomarkers and potential therapeutic targets (at various disease stages) may result in improved patient outcome (3,4). It is therefore important to investigate the molecular mechanisms underpinning the development and progression of prostate cancer, as this may catalyze the identification of novel therapeutic targets (5,6).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of contactin‑1 expression promotes prostate cancer progression

et al. 2019

View full text Add to dashboard Cite

Contactin-1 (CNTN-1) has been reported to serve an oncogenic role in several cancer types. However, detailed mechanisms describing the influence of CNTN-1 in prostate cancer progression have not yet been elucidated. The present study aimed to determine the clinical significance of CNTN-1 expression in prostate cancer progression, and also to investigate the regulatory role of CNTN-1 in the proliferation, migration and invasive ability of prostate cancer cells. The results of the present study indicated that expression levels of CNTN-1 were significantly higher in prostate cancer tissues compared with adjacent normal tissues. Moreover, a high expression level of CNTN-1 was positively correlated with tumor size, stage and metastasis, as well as a poorer prognosis in patients with prostate cancer. Furthermore, CNTN-1-knockdown in prostate cancer cells (using short hairpin RNA) resulted in the significant inhibition of cancer cell proliferation, colony formation, migration and invasiveness. Silencing of CNTN-1 expression also suppressed epithelial-mesenchymal transition in prostate cancer cells via the upregulation of E-cadherin, and the downregulation of N-cadherin and vimentin expression. Inhibition of CNTN-1 expression also reduced the activity of the PI3K/AKT signaling pathway in prostate cancer cells. Thus, it was demonstrated that CNTN-1 expression is upregulated, and plays an oncogenic role, in prostate cancer cells. The results of the current study suggest that CNTN-1 may represent a promising therapeutic target, potentially improving the treatment of patients with prostate cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

Upregulation of contactin‑1 expression promotes prostate cancer progression

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Con rmed by our further protein detection, SRC3 (not SRC1 or SRC2) is remarkably diminished, with the increase of THB concentration. It is well known that SRC3, a member of the p160 SRC family (including SRC1, SRC2 and SRC3) regulates the transcriptional functions of nuclear receptors and other transcription factors, modulating cell proliferation, survival and growth [23,24]. And the overexpression of SRC3 was reported to induce tumorigenesis and chemoresistance by modulating cancer-related signaling pathways, promoting the expression of antiapoptotic proteins and inhibiting the expression of pro-apoptotic proteins [25].…”

Section: Discussionmentioning

confidence: 99%

Thevebioside, the Active Ingredient of Traditional Chinese Medicine, Inhibits SRC3 Mediated Signaling by Ubiquitination to Induce NSCLC Cells Apoptosis

Yao

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background:The high incidence and mortality of lung cancer has been a widespread concern in the world, among which non-small cell lung cancer (NSCLC)accounts for more than 85% of lung cancer, and its 5-year prognosis is pretty poor. Accumulating studies have shown that traditional Chinese medicine (TCM) and its active ingredients have shown good anti-tumor activity. Based on the results of our previous high-throughput screening, it was the first time to find that Thevebioside (THB, an active ingredient from TCM) is sensitive to NSCLC cells, and then we will still the first to reveal the underling mechanism of its tumor suppressive activity.Methods: In this study, MTT and colony formation assay were used to detect cell growth. Annexin V/ propidium iodide, Hoechst 33342 were applied to test the process of cellular apoptosis or cell cycle arrest which determined by flow cytometry in NSCLC (A549 and H460) cells. qRT-PCR and Western blot was utilized to value the level of expression of SRC&(SRC1-3) and apoptosis related proteins. The ubiquitination degradation of SRC3 was through proteasome dependent pathway were examined by the usage of CHX and MG132 and the co-immunoprecipitation assay. The anticancer activity of THB, Neritaloside，Odoroside H and digoxin in vivo were monitored in nude mice by subcutaneous inoculation or intrapulmonary injection of A549 cells and then administrated these agents (2 mg/ kg or 4mg/kg) by intraperitoneal injection three times a week for 30 days. Tumor growth was monitored by a luciferase living imaging system. Body weight of mice and tumor volume were measured weekly. The survival carve was recorded. Pathological histology of liver, kidney and heart were detected by H&E staining, and its functions were tested by ELISA. Results：THB effectively inhibits the outgrowth of NSCLC cells (A549 and H460) by inducing cellular apoptosis. SRC-3 was significantly down-regulated after THB treatment dependent on ubiquitin-proteasome-mediated degradation, which subsequently inhibited the AKT signaling pathway to promte apoptosis. Animal study supported in vitro results, showing THB had a good suppressive effect on tumor growth. Besides, it also indicated that THB without overt cytotoxic effect on liver, kidney and heart.Conclusion：THB , as an active extract from TCM，exerted inhibitory effect on tumor growth of NSCLC by down-regulating the expression of SCR-3 rely on the ubiquitin-proteasome degradation pathway, thereby inhibiting the AKT signaling to induce cellular apoptosis , with minimal toxicity.

show abstract

“…In recent years, a large number of lncRNAs have been demonstrated to participate in various cellular biological processes, such as cell proliferation, differentiation, apoptosis, cell cycle, motility, and tumourigenesis (6,7). A number of lncRNAs have been identified as oncogenes or tumor suppressors in human cancers, including melanoma (8,9). For instance, the lncRNA growth arrest-specific 5 serves an inhibitory role in melanoma via regulating gelatinase A and B both in vitro and in vivo (10).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of lncRNA‑UCA1 inhibits the proliferation and migration of melanoma cells through modulating the miR‑28‑5p/HOXB3 axis

et al. 2019

View full text Add to dashboard Cite

Long non-coding RNA urothelial carcinoma-associated 1 (UCA1) functions as an oncogene in different human cancers, including melanoma. However, the molecular mechanism of UCA1 underlying melanoma progression still remains largely unknown. In the present study, reverse transcription quantitative polymerase chain reaction and western blot analyses were used to examine the mRNA and protein expression levels, respectively. Cell Counting Kit-8 and wound healing assays were conducted to study cell proliferation and migration, respectively. A luciferase reporter assay was used to confirm the targeting relationship. It was demonstrated that UCA1 expression was increased in melanoma tissues and cell lines. In addition, UCA1 expression was higher in melanoma tissues at stage III-IV than in tissues at stage I-II. Inhibition of UCA1 expression markedly reduced melanoma cell proliferation and migration. Further investigation revealed that UCA1 functioned in melanoma cells through directly binding with microRNA (miR)-28-5p. The expression of miR-28-5p was significantly reduced in melanoma tissues and had an inverse correlation with UCA1 expression. In addition, miR-28-5p expression was higher in melanoma tissues at advanced stages than in stage I-II tissues. Furthermore, homeobox (HOX)B3 was identified as a target gene of miR-28-5p in melanoma cells, and HOXB3 overexpression reversed the suppressive effects of UCA1 downregulation on melanoma cell proliferation and migration. Finally, HOXB3 was upregulated in melanoma tissues compared with its expression in adjacent tissues, and HOXB3 expression was increased in melanoma tissues at advanced stages. Taken together, the regulatory network of the UCA1/miR-28-5p/HOXB3 axis in melanoma was demonstrated for the first time in the present study, expanding the understanding of the molecular mechanism underlying melanoma progression. Future studies may further confirm the function of this signaling pathway in vivo.

show abstract

Oncogenic non-coding RNA NEAT1 promotes the prostate cancer cell growth through the SRC3/IGF1R/AKT pathway

Cited by 53 publications

References 33 publications

Upregulation of contactin‑1 expression promotes prostate cancer progression

Upregulation of contactin‑1 expression promotes prostate cancer progression

Thevebioside, the Active Ingredient of Traditional Chinese Medicine, Inhibits SRC3 Mediated Signaling by Ubiquitination to Induce NSCLC Cells Apoptosis

Knockdown of lncRNA‑UCA1 inhibits the proliferation and migration of melanoma cells through modulating the miR‑28‑5p/HOXB3 axis

Contact Info

Product

Resources

About