Long Non-coding RNA LINC00115 Contributes to the Progression of Colorectal Cancer by Targeting miR-489-3p via the PI3K/AKT/mTOR Pathway.
TL;DR: It is demonstrated that LINC00115 serves as an oncogene in CRC metastasis and deeper understanding of the LINC 00115/miR-489-3p axis might provide potential therapeutic targets against CRC metastases.
Abstract: Long non-coding RNAs (lncRNAs) are tumor-related regulators and have been found to be involved in the underlying molecular mechanisms of colorectal cancer (CRC). However, the role of lncRNA LINC00115 during CRC progression is not entirely elucidated. In this study, we discovered that LINC00115 was significantly overexpressed in CRC, and its overexpression predicted poor patient outcomes. Downregulation of LINC00115 markedly inhibited CRC cell proliferation, increased cell apoptosis, and suppressed cell migration and invasion. Moreover, downregulation of LINC00115 led to the inactivation of PI3K/AKT/mTOR signaling. Bioinformatics analysis identified miR-489-3p as a candidate target of LINC00115. Furthermore, we revealed an inverse correlation between LINC00115 and miR-489-3p in CRC tissues. Importantly, by luciferase reporter assay, we found that miR-489-3p might directly target LINC00115, and downregulation of miR-489-3p could rescue the biological effects induced by the absence of LINC0015. In conclusion, our findings demonstrated that LINC00115 serves as an oncogene in CRC metastasis. Deeper understanding of the LINC00115/miR-489-3p axis might provide potential therapeutic targets against CRC metastasis.
Citations
More filters
TL;DR: The potential function of miRNA-489 as tumor-suppressor in various cancers is described in this article, where the miRNA is able to sensitize cancer cells into chemotherapy by disrupting molecular pathways involved in cancer growth such as PI3K/Akt, and induction of apoptosis.
30 citations
TL;DR: In this paper, a review summarizes the major mechanisms of long non-coding RNAs in CRC metastasis and proposes lncRNAs as potential therapeutic targets for CRC and molecular markers for early diagnosis.
Abstract: Colorectal cancer (CRC) is one of the most common gastrointestinal cancers, with extremely high rates of morbidity and mortality. The main cause of death in CRC is distant metastasis; it affects patient prognosis and survival and is one of the key challenges in the treatment of CRC. Long non-coding RNAs (lncRNAs) are a group of non-coding RNA molecules with more than 200 nucleotides. Abnormal lncRNA expression is closely related to the occurrence and progression of several diseases, including cancer. Recent studies have shown that numerous lncRNAs play pivotal roles in the CRC metastasis, and reversing the expression of these lncRNAs through artificial means can reduce the malignant phenotype of metastatic CRC to some extent. This review summarizes the major mechanisms of lncRNAs in CRC metastasis and proposes lncRNAs as potential therapeutic targets for CRC and molecular markers for early diagnosis.
18 citations
TL;DR: Wang et al. as discussed by the authors showed that LINC00115 was significantly upregulated in prostate cancer tissues, which was significantly associated with a poor prognosis for prostate cancer patients. And they provided clues that Linc00115 may be a promising novel therapeutic target for men with prostate cancer.
Abstract: Prostate cancer is the second most frequent malignancy in men worldwide, and its incidence is increasing. Therefore, it is urgently required to clarify the underlying mechanisms of prostate cancer. Although the long non-coding RNA LINC00115 was identified as an oncogene in several cancers, the expression and function of LINC00115 in prostate cancer have not been explored. Our results showed that LINC00115 was significantly up-regulated in prostate cancer tissues, which was significantly associated with a poor prognosis for prostate cancer patients. Functional studies showed that knockdown LINC00115 inhibited cell proliferation and invasion. In addition, LINC00115 served as a competing endogenous RNA (ceRNA) through sponging miR-212-5p to release Frizzled Family Receptor 5 (FZD5) expression. The expression of miR-212-5p was noticeably low in tumour tissues, and FZD5 expression level was down-regulated with the knockdown of LINC00115. Knockdown LINC00115 inhibited the Wnt/β-catenin signalling pathway by inhibiting the expression of FZD5. Rescue experiments further showed that LINC00115 inhibits prostate cancer cell proliferation and invasion via targeting miR-212-5p/ FZD5/ Wnt/β-catenin axis. The present study provided clues that LINC00115 may be a promising novel therapeutic target for prostate cancer patients.
14 citations
TL;DR: In this paper, the authors summarize the epigenetic findings linked to miRNAome in the maintenance and regulation of colorectal cancer stem cells, including their relationships with different signaling pathways, which should help to identify specific diagnostic, prognostic, and predictive biomarkers for CRC, but also develop innovative CCSC-targeted therapies.
Abstract: Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and about 20% is metastatic at diagnosis and untreatable. Increasing evidence suggests that the heterogeneous nature of CRC is related to colorectal cancer stem cells (CCSCs), a small cells population with stemness behaviors and responsible for tumor progression, recurrence, and therapy resistance. Growing knowledge of stem cells (SCs) biology has rapidly improved uncovering the molecular mechanisms and possible crosstalk/feedback loops between signaling pathways that directly influence intestinal homeostasis and tumorigenesis. The generation of CCSCs is probably connected to genetic changes in members of signaling pathways, which control self-renewal and pluripotency in SCs and then establish function and phenotype of CCSCs. Particularly, various deregulated CCSC-related miRNAs have been reported to modulate stemness features, controlling CCSCs functions such as regulation of cell cycle genes expression, epithelial-mesenchymal transition, metastasization, and drug-resistance mechanisms. Primarily, CCSC-related miRNAs work by regulating mainly signal pathways known to be involved in CCSCs biology. This review intends to summarize the epigenetic findings linked to miRNAome in the maintenance and regulation of CCSCs, including their relationships with different signaling pathways, which should help to identify specific diagnostic, prognostic, and predictive biomarkers for CRC, but also develop innovative CCSCs-targeted therapies.
7 citations
TL;DR: In this article, the authors conducted a comprehensive ccRCC RNA-seq analysis using The Cancer Genome Atlas data to establish an m6A-related lncRNA prognostic signature (m6A -RLPS) for clear-cell renal cell carcinoma (ccRCC).
Abstract: Increasing evidence suggests that N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play important roles in cancer progression and immunotherapeutic efficacy in clear-cell renal cell carcinoma (ccRCC). In this study, we conducted a comprehensive ccRCC RNA-seq analysis using The Cancer Genome Atlas data to establish an m6A-related lncRNA prognostic signature (m6A-RLPS) for ccRCC. Forty-four prognostic m6A-related lncRNAs (m6A-RLs) were screened using Pearson correlation analysis (|R| > 0.7, p < 0.001) and univariable Cox regression analysis (p < 0.01). Using consensus clustering, the patients were divided into two clusters with different overall survival (OS) rates and immune status according to the differential expression of the lncRNAs. Gene set enrichment analysis corroborated that the clusters were enriched in immune-related activities. Twelve prognostic m6A-RLs were selected and used to construct the m6A-RLPS through least absolute shrinkage and selection operator Cox regression. We validated the differential expression of the 12 lncRNAs between tumor and non-cancerous samples, and the expression levels of four m6A-RLs were further validated using Gene Expression Omnibus data and Lnc2Cancer 3.0 database. The m6A-RLPS was verified to be an independent and robust predictor of ccRCC prognosis using univariable and multivariable Cox regression analyses. A nomogram based on age, tumor grade, clinical stage, and m6A-RLPS was generated and showed high accuracy and reliability at predicting the OS of patients with ccRCC. The prognostic signature was found to be strongly correlated to tumor-infiltrating immune cells and immune checkpoint expression. In conclusion, we established a novel m6A-RLPS with a favorable prognostic value for patients with ccRCC. The 12 m6A-RLs included in the signature may provide new insights into the tumorigenesis and allow the prediction of the treatment response of ccRCC.
6 citations
References
More filters
TL;DR: The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak.
Abstract: Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.
16,028 citations
TL;DR: Dysregulation of these ncRNAs is being found to have relevance not only to tumorigenesis, but also to neurological, cardiovascular, developmental and other diseases, and there is great interest in therapeutic strategies to counteract these perturbations.
Abstract: The role of non-coding RNAs (ncRNAs) in disease is best understood for microRNAs in cancer. However, there is increasing interest in the disease-related roles of other ncRNAs — including piRNAs, snoRNAs, T-UCRs and lncRNAs — and in using this knowledge for therapy.
4,016 citations
"Long Non-coding RNA LINC00115 Contr..." refers background in this paper
...…RNAs (ncRNAs), including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), have been recently reported to be involved in the regulation of protein-coding genes in both physiological and pathological conditions (Kapranov et al., 2007; Esteller, 2011; Cech and Steitz, 2014)....
[...]
...Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), have been recently reported to be involved in the regulation of protein-coding genes in both physiological and pathological conditions (Kapranov et al., 2007; Esteller, 2011; Cech and Steitz, 2014)....
[...]
TL;DR: Overall CRC incidence in individuals ages ≥50 years declined from 2009 to 2013 in every state except Arkansas, with the decrease exceeding 5% annually in 7 states; however, rectal tumor incidence in those ages 50 to 64 years was stable in most states.
Abstract: Colorectal cancer (CRC) is one of the most common malignancies in the United States. Every 3 years, the American Cancer Society provides an update of CRC incidence, survival, and mortality rates and trends. Incidence data through 2013 were provided by the Surveillance, Epidemiology, and End Results program, the National Program of Cancer Registries, and the North American Association of Central Cancer Registries. Mortality data through 2014 were provided by the National Center for Health Statistics. CRC incidence rates are highest in Alaska Natives and blacks and lowest in Asian/Pacific Islanders, and they are 30% to 40% higher in men than in women. Recent temporal patterns are generally similar by race and sex, but differ by age. Between 2000 and 2013, incidence rates in adults aged ≥50 years declined by 32%, with the drop largest for distal tumors in people aged ≥65 years (incidence rate ratio [IRR], 0.50; 95% confidence interval [95% CI], 0.48-0.52) and smallest for rectal tumors in ages 50 to 64 years (male IRR, 0.91; 95% CI, 0.85-0.96; female IRR, 1.00; 95% CI, 0.93-1.08). Overall CRC incidence in individuals ages ≥50 years declined from 2009 to 2013 in every state except Arkansas, with the decrease exceeding 5% annually in 7 states; however, rectal tumor incidence in those ages 50 to 64 years was stable in most states. Among adults aged <50 years, CRC incidence rates increased by 22% from 2000 to 2013, driven solely by tumors in the distal colon (IRR, 1.24; 95% CI, 1.13-1.35) and rectum (IRR, 1.22; 95% CI, 1.13-1.31). Similar to incidence patterns, CRC death rates decreased by 34% among individuals aged ≥50 years during 2000 through 2014, but increased by 13% in those aged <50 years. Progress against CRC can be accelerated by increasing initiation of screening at age 50 years (average risk) or earlier (eg, family history of CRC/advanced adenomas) and eliminating disparities in high-quality treatment. In addition, research is needed to elucidate causes for increasing CRC in young adults. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:177-193. © 2017 American Cancer Society.
3,220 citations
TL;DR: The pathway of ncRNA research is described, where every established "rule" seems destined to be overturned.
1,875 citations
TL;DR: Observations suggest that genomic architecture is not colinear, but is instead interleaved and modular, and that the same genomic sequences are multifunctional: that is, used for multiple independently regulated transcripts and as regulatory regions.
Abstract: Recent evidence of genome-wide transcription in several species indicates that the amount of transcription that occurs cannot be entirely accounted for by current sets of genome-wide annotations. Evidence indicates that most of both strands of the human genome might be transcribed, implying extensive overlap of transcriptional units and regulatory elements. These observations suggest that genomic architecture is not colinear, but is instead interleaved and modular, and that the same genomic sequences are multifunctional: that is, used for multiple independently regulated transcripts and as regulatory regions. What are the implications and consequences of such an interleaved genomic architecture in terms of increased information content, transcriptional complexity, evolution and disease states?
696 citations