Targeting Long Non-coding RNA to Therapeutically Regulate Gene Expression in Cancer

Fu, Da; Shi, Yi; Liu, Ji‐Bin; Wu, Ting‐Miao; Jia, Chengyou; Yang, Haojie; Zhang, Dandan; Yang, Xiaoli; Wang, Huimin; Ma, Yu‐Shui

doi:10.1016/j.omtn.2020.07.005

Cited by 63 publications

(50 citation statements)

References 135 publications

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“…A number of lncRNAs have been identified as potential predictive and prognostic biomarkers including SChLAP1, UCA1 and PCAT14 ( Mehra et al, 2016 ; Fotouhi Ghiam et al, 2017 ; White et al, 2017 ). Further work is exploring lncRNAs as therapeutic targets in PCa using small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs) and small molecule inhibitors ( Fu et al, 2020 ). Therefore, there is significant interest in the role ncRNAs may play in the future management of PCa.…”

Section: Discussionmentioning

confidence: 99%

Differential CircRNA Expression Signatures May Serve as Potential Novel Biomarkers in Prostate Cancer

Greene

Baird

Lim

et al. 2021

Front. Cell Dev. Biol.

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Circular RNAs (circRNAs), a recently discovered non-coding RNA, have a number of functions including the regulation of miRNA expression. They have been detected in a number of malignancies including prostate cancer (PCa). The differential expression pattern of circRNAs associated with PCa and androgen receptor (AR) status was investigated in this study. circRNA profiling was performed using a high throughout microarray assay on a panel of prostate cell lines, which consisted of normal, benign, and malignant cells (n = 9). circRNAs were more commonly significantly up-regulated (p < 0.05) than downregulated in malignant cell lines (n = 3,409) vs. benign cell lines (n = 2,949). In a grouped analysis based on AR status, there were 2,127 down-regulated circRNAs in androgen independent cell lines compared to 2,236 in androgen dependent cell lines, thus identifying a potential circRNA signature reflective of androgen dependency. Through a bioinformatics approach, the parental genes associated with the top 10 differentially expressed circRNAs were identified such as hsa_circ_0064644, whose predicted parental gene target is RBMS3, and hsa_circ_0060539, whose predicted gene target is SDC4. Furthermore, we identified three circRNAs associated with the parental gene Caprin1 (hsa_circ_0021652, hsa_circ_0000288, and hsa_circ_0021647). Other studies have shown the importance of Caprin1 in PCa cell survival and drug resistance. Given the modified circRNA expression signatures identified here, these hypothesis generating results suggest that circRNAs may serve as potential putative diagnostic and predictive markers in PCa. However, further validation studies are required to assess the true potential of these markers in the clinical setting.

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Section: Discussionmentioning

confidence: 99%

Differential CircRNA Expression Signatures May Serve as Potential Novel Biomarkers in Prostate Cancer

Greene

Baird

Lim

et al. 2021

Front. Cell Dev. Biol.

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“…Recently, lncRNAs have attracted the attention of more and more researchers. 8 , 27 , 28 An increasing number of studies have reported that lncRNAs are dysregulated and are essential regulators and tumor facilitators in cervical cancer. 29 Hence, identifying the lncRNAs involved in cervical cancer and exploring their detailed roles will be beneficial for developing effective targets to guide cancer diagnosis, prevention, and treatment.…”

Section: Discussionmentioning

confidence: 99%

Long Intergenic Non-Coding RNA LINC00885 Promotes Tumorigenesis of Cervical Cancer by Upregulating MACC1 Expression Through Serving as a Competitive Endogenous RNA for microRNA-432-5p

Chen

Chi

Chen

et al. 2021

CMAR

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Purpose Long intergenic non-protein coding RNA 885 (LINC00885) has been well studied in breast cancer; however, its contribution in cervical cancer remains unclear. In this study, we aimed to determine the detailed functions of LINC00885 in cervical cancer and elucidate the underlying molecular regulation mechanism. Methods The expression status of LINC00885 in cervical cancer was determined using reverse transcription-quantitative polymerase chain reaction and by searching The Cancer Genome Atlas database. The detailed functions of LINC00885 in cervical cancer cells were confirmed using Cell Counting Kit 8 assay, flow cytometry analysis, Transwell cell migration and invasion assays, and tumor xenograft assay. Mechanistic experiments included bioinformatics prediction, RNA immunoprecipitation, luciferase reporter assay, and rescue experiments. Results LINC00885 was clearly overexpressed in cervical cancer, which was linked with unfavorable clinical outcomes. Functionally, LINC00885 deficiency suppressed cervical cancer cell proliferation, migration, and invasion but stimulated cell apoptosis in vitro. Furthermore, loss of LINC00885 restricted the growth of cervical cancer cells in vivo. Mechanistically, LINC00885 functioned as a competitive endogenous RNA for microRNA-432-5p (miR-432-5p) in cervical cancer. Furthermore, metastasis-associated colon cancer 1 (MACC1) was confirmed as the direct target of miR-432-5p, and LINC00885 could enhance MACC1 expression by sequestering miR-432-5p. Rescue experiments revealed that silencing of miR-432-5p or upregulation of MACC1 expression could effectively counteract the restrained aggressive properties of cervical cancer cells induced by LINC00885 deficiency. Conclusion LINC00885 upregulated MACC1 expression in cervical cancer cells by sponging miR-432-5p, thereby promoting cancer progression. The LINC00885/miR-432-5p/MACC1 pathway may help in the identification of potential prognostic biomarkers and therapeutic targets in cervical cancer.

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“…LncRNA was initially thought to be the noise of gene transcription because it does not have an open reading frame and rarely participates in encoding proteins. However, lncRNAs have been confirmed in recent years for the regulation of various diseases by binding to microRNAs or proteins, thereby participating in the occurrence, progression, and prognosis of diseases (5). The abnormal expression of lncRNA plays an important role in various cancers, such as hepatocellular carcinoma, breast cancer, prostate cancer, and non-small-cell lung cancer (NSCLC) (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

“…However, lncRNAs have been confirmed in recent years for the regulation of various diseases by binding to microRNAs or proteins, thereby participating in the occurrence, progression, and prognosis of diseases ( 5 ). The abnormal expression of lncRNA plays an important role in various cancers, such as hepatocellular carcinoma, breast cancer, prostate cancer, and non-small-cell lung cancer (NSCLC) ( 5 – 7 ). Therefore, it has been proposed that lncRNAs can become tumor biomarkers.…”

Section: Introductionmentioning

confidence: 99%

LncRNA SNHG8 Promotes Proliferation and Inhibits Apoptosis of Diffuse Large B-Cell Lymphoma via Sponging miR-335-5p

Wang

et al. 2021

Front. Oncol.

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Long-chain non-coding RNAs (LncRNAs) are expressed in diffuse large B-cell lymphoma (DLBCL) tissues and have played a regulatory role in DLBCL with a cancer-promoting effect. In this study, the role of LncRNA SNHG8 in the regulation of DLBCL cells is investigated, and its underlying mechanism is explored. The database of the Gene Expression Profiling Interactive Analysis (GEPIA) was searched, and the expression of SNHG8 in DLBCL and normal tissues was examined. The expression of SNHG8 was evaluated in several DLBCL cell lines and a normal lymphocyte cell line. It was found that SNHG8 was overexpressed in DLBCL tissues and cells in comparison with their normal counterparts. The short hairpin RNA (shRNA) plasmids of SNHG8 were transfected into DLBCL cells to knockdown the expression of SNHG8, followed by assays of proliferation, colony formation, apoptosis, and related protein expression. The results showed that the knockdown of SNHG8 significantly inhibited DLBCL cell proliferation and colony formation while promoting cell apoptosis. Moreover, the knockdown of SNHG8 reduced the expression of Ki-67, proliferating cell nuclear antigen (PCNA), and Bcl-2 and enhanced the expression of Bax and cleaved caspase 3/9. MiR-335-5p was predicted to be a potential target of SNHG8 by using the bioinformatics analysis, and the interaction between the two was validated by using the dual luciferase assay. In addition, the knockdown of SNHG8 increased the level of miR-335-5p, whereas miR-335-5p mimic decreased the expression of SNHG8. Finally, U2932 cells were co-transfected with or without sh-SNHG8 and miR-335-5p inhibitors, whose proliferation, colony formation, and apoptosis were determined subsequently. It was demonstrated that the presence of an miR-335-5p inhibitor partially canceled the inhibitory effects of the knockdown of SNHG8 on DLBCL cell proliferation and colony formation and the stimulating effects of the knockdown of SNHG8 on cell apoptosis. Taken together, our study suggests that lncRNA SNHG8 exerts a cancer-promoting effect on DLBCL via targeting miR-335-5p.

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Targeting Long Non-coding RNA to Therapeutically Regulate Gene Expression in Cancer

Cited by 63 publications

References 135 publications

Differential CircRNA Expression Signatures May Serve as Potential Novel Biomarkers in Prostate Cancer

Differential CircRNA Expression Signatures May Serve as Potential Novel Biomarkers in Prostate Cancer

Long Intergenic Non-Coding RNA LINC00885 Promotes Tumorigenesis of Cervical Cancer by Upregulating MACC1 Expression Through Serving as a Competitive Endogenous RNA for microRNA-432-5p

LncRNA SNHG8 Promotes Proliferation and Inhibits Apoptosis of Diffuse Large B-Cell Lymphoma via Sponging miR-335-5p

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