Long Noncoding RNA LINC00958 Suppresses Apoptosis and Radiosensitivity of Colorectal Cancer Through Targeting miR-422a
TL;DR: LINC00958 promoted MAPK1 expression and cell proliferation and suppressed apoptosis and the radiosensitivity through targeting miR-422a, highlighting a potential biomarker for the prognosis and treatment of colorectal cancer.
Abstract: Background Long noncoding RNAs (lncRNAs) have been elucidated to participate in the development and progression of various cancers. In this study, we aimed to explore the underlying functions and mechanisms of LINC00958 in colorectal cancer. Methods LINC00958 expression in colorectal cancer tissues was examined by qRT-PCR. The correlations between LINC00958 expression and clinical characteristics and prognosis were evaluated. The biological functions of LINC00958 were detected by CCK-8, MTT, colony formation and flow cytometric analyses. RNA pulldown, RIP and luciferase reporter assays were used to confirm the regulatory effects of LINC00958 on miR-422a. Rescue experiments were performed to detect the effects of miR-422a on the roles of LINC00958. Results LINC00958 was upregulated in colorectal cancer tissues and cell lines. High LINC00958 levels were positively associated with T stage and predicted poor prognosis. Cell experiments showed that LINC00958 promoted cell proliferation and suppressed apoptosis and sensitivity to radiotherapy in vitro and promoted tumor growth in vivo. Bioinformatics analysis predicted the binding site of miR-422a on LINC00958. Mechanistically, RNA pulldown, RIP and luciferase reporter assays demonstrated that LINC00958 specifically targeted miR-422a. In addition, we found that miR-422a suppressed MAPK1 expression by directly binding to the 3'-UTR of MAPK1, thereby inhibiting cell proliferation and enhancing cell apoptosis and radiosensitivity. Furthermore, miR-422a rescued the roles of LINC00958 in promoting MAPK1 expression and cell proliferation and decreasing cell apoptosis and radiosensitivity. Conclusions LINC00958 promoted MAPK1 expression and cell proliferation and suppressed cell apoptosis and radiosensitivity by targeting miR-422a, which suggests that it is a potential biomarker for the prognosis and treatment of colorectal cancer.
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TL;DR: In this paper , the function and mechanisms of lncRNAs to regulate the expression of genes that are involved directly or indirectly in controlling cellular apoptosis in colorectal cancer (CRC).
Abstract: Long non-coding RNA (LncRNA) is a novel and diverse class of regulatory transcripts that are frequently dysregulated in numerous tumor types. LncRNAs are involved in a complicated molecular network, regulating gene expression, and modulating diverse cellular activities in different cancers including colorectal cancer (CRC). Evidence indicates that lncRNAs can be used as a potential biomarker for the prognosis and diagnosis of CRC as they are aberrantly expressed in CRC cells. The high expression or silencing of lncRNAs is associated with cell proliferation, invasion, metastasis, chemoresistance and apoptosis in CRC. LncRNAs exert both pro-apoptotic and anti-apoptotic functions in CRC. The expression of some oncogene lncRNAs is upregulated which leads to the inhibition of apoptotic pathways, similarly, the tumor suppressor lncRNAs are downregulated in CRC. In this review, we describe the function and mechanisms of lncRNAs to regulate the expression of genes that are involved directly or indirectly in controlling cellular apoptosis in CRC. Furthermore, we also discussed the different apoptotic pathways in normal cells and the mechanisms by which CRC evade apoptosis.
9 citations
TL;DR: In this article , the function and mechanisms of lncRNAs to regulate the expression of genes that are involved directly or indirectly in controlling cellular apoptosis in colorectal cancer (CRC).
Abstract: Long non-coding RNA (LncRNA) is a novel and diverse class of regulatory transcripts that are frequently dysregulated in numerous tumor types. LncRNAs are involved in a complicated molecular network, regulating gene expression, and modulating diverse cellular activities in different cancers including colorectal cancer (CRC). Evidence indicates that lncRNAs can be used as a potential biomarker for the prognosis and diagnosis of CRC as they are aberrantly expressed in CRC cells. The high expression or silencing of lncRNAs is associated with cell proliferation, invasion, metastasis, chemoresistance and apoptosis in CRC. LncRNAs exert both pro-apoptotic and anti-apoptotic functions in CRC. The expression of some oncogene lncRNAs is upregulated which leads to the inhibition of apoptotic pathways, similarly, the tumor suppressor lncRNAs are downregulated in CRC. In this review, we describe the function and mechanisms of lncRNAs to regulate the expression of genes that are involved directly or indirectly in controlling cellular apoptosis in CRC. Furthermore, we also discussed the different apoptotic pathways in normal cells and the mechanisms by which CRC evade apoptosis.
9 citations
TL;DR: The role of long non-coding RNA (lncRNA) in cancer radioresistance/radiosensitivity is demonstrated and lncRNAs are important regulators involved in tumor Radioresistance\sensitivity.
Abstract: Background and purpose: Radioresistance remains a significant challenge in tumor therapy. This systematic review aims to demonstrate the role of long non-coding RNA (lncRNA) in cancer radioresistance/radiosensitivity. Material and methods: The electronic databases Pubmed, Embase, and Google Scholar were searched from January 2000 to December 2021 to identify studies addressing the mechanisms of lncRNAs in tumor radioresistance/sensitivity, each of which required both in vivo and in vitro experiments. Results: Among the 87 studies identified, lncRNAs were implicated in tumor radioresistance/sensitivity mainly in three paradigms. 1) lncRNAs act on microRNA (miRNA) by means of a sponge, and their downstream signals include some specific molecular biological processes (DNA repair and chromosome stabilization, mRNA or protein stabilization, cell cycle and proliferation, apoptosis-related pathways, autophagy-related pathways, epithelial-mesenchymal transition (EMT), cellular energy metabolism) and some signaling mediators (transcription factors, kinases, some important signal transduction pathways) that regulate various biological processes. 2) lncRNAs directly interact with proteins, affecting the cell cycle and autophagy to contribute to tumor radioresistance. 3) lncRNAs act like transcription factors to initiate downstream signaling pathways and participate in tumor radioresistance. Conclusion: lncRNAs are important regulators involved in tumor radioresistance\sensitivity. Different lncRNAs may participate in the radioresistance with the same regulatory paradigm, and the same lncRNAs may also participate in the radioresistance in different ways. Future research should focus more on comprehensively characterizing the mechanisms of lncRNAs in tumor radioresistance to help us identify corresponding novel biomarkers and develop new lncRNA-based methods to improve radioresistance.
9 citations
TL;DR: Long non-coding RNAs (lncRNAs), a class of RNA transcripts longer than 200 nucleotides, do not encode proteins; however, they encode small peptides and micropeptides that act as bioactive peptides with notable effects in regulating the progression of malignant tumors, such as lung and colorectal cancers, and affecting patient prognosis as discussed by the authors .
6 citations
TL;DR: The biological functions and underlying mechanisms of ncRNAs (primarily lncRNA, miRNA, and circRNA) in the regulation of the radiosensitivity of CRC are discussed and studies that examined nc RNAs as biomarkers of response to radiation and as therapeutic targets for enhancing radiosensitivity are evaluated.
Abstract: Colorectal cancer (CRC) is a global public health concern because of its high prevalence and mortality. Although radiotherapy is a key method for treating CRC, radioresistance is an obstacle to radiotherapy use. The molecular mechanisms underlying the radioresistance of CRC remain unclear. Increasing evidence has revealed the multiple regulatory functions of non-coding RNAs (ncRNAs) in numerous malignancies, including CRC. Several ncRNAs have been reported to be involved in the determination of radiosensitivity of CRC cells, and some have excellent potential to be prognostic biomarkers or therapeutic targets in CRC treatment. The present review discusses the biological functions and underlying mechanisms of ncRNAs (primarily lncRNA, miRNA, and circRNA) in the regulation of the radiosensitivity of CRC. We also evaluate studies that examined ncRNAs as biomarkers of response to radiation and as therapeutic targets for enhancing radiosensitivity.
3 citations
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TL;DR: A status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions.
Abstract: This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions There will be an estimated 181 million new cancer cases (170 million excluding nonmelanoma skin cancer) and 96 million cancer deaths (95 million excluding nonmelanoma skin cancer) in 2018 In both sexes combined, lung cancer is the most commonly diagnosed cancer (116% of the total cases) and the leading cause of cancer death (184% of the total cancer deaths), closely followed by female breast cancer (116%), prostate cancer (71%), and colorectal cancer (61%) for incidence and colorectal cancer (92%), stomach cancer (82%), and liver cancer (82%) for mortality Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality) Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts CA: A Cancer Journal for Clinicians 2018;0:1-31 © 2018 American Cancer Society
58,675 citations
TL;DR: Slow momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers, and it is notable that long‐term rapid increases in liver cancer mortality have attenuated in women and stabilized in men.
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 population-based cancer occurrence. Incidence data (through 2016) 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 (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.
15,080 citations
TL;DR: Progress against CRC can be accelerated by increasing access to guideline‐recommended screening and high‐quality treatment, particularly among Alaska Natives, and elucidating causes for rising incidence in young and middle‐aged adults.
Abstract: Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Every 3 years, the American Cancer Society provides an update of CRC occurrence based on incidence data (available through 2016) from population-based cancer registries and mortality data (through 2017) from the National Center for Health Statistics. In 2020, approximately 147,950 individuals will be diagnosed with CRC and 53,200 will die from the disease, including 17,930 cases and 3,640 deaths in individuals aged younger than 50 years. The incidence rate during 2012 through 2016 ranged from 30 (per 100,000 persons) in Asian/Pacific Islanders to 45.7 in blacks and 89 in Alaska Natives. Rapid declines in incidence among screening-aged individuals during the 2000s continued during 2011 through 2016 in those aged 65 years and older (by 3.3% annually) but reversed in those aged 50 to 64 years, among whom rates increased by 1% annually. Among individuals aged younger than 50 years, the incidence rate increased by approximately 2% annually for tumors in the proximal and distal colon, as well as the rectum, driven by trends in non-Hispanic whites. CRC death rates during 2008 through 2017 declined by 3% annually in individuals aged 65 years and older and by 0.6% annually in individuals aged 50 to 64 years while increasing by 1.3% annually in those aged younger than 50 years. Mortality declines among individuals aged 50 years and older were steepest among blacks, who also had the only decreasing trend among those aged younger than 50 years, and excluded American Indians/Alaska Natives, among whom rates remained stable. Progress against CRC can be accelerated by increasing access to guideline-recommended screening and high-quality treatment, particularly among Alaska Natives, and elucidating causes for rising incidence in young and middle-aged adults.
2,928 citations
TL;DR: A lipogenesis-related lncRNA, LINC00958, whose expression was upregulated in HCC cell lines and tissues was identified, providing a novel prognostic indicator and promising nanotherapeutic target.
Abstract: Long non-coding RNAs (lncRNAs) possess significant regulatory functions in multiple biological and pathological processes, especially in cancer. Dysregulated lncRNAs in hepatocellular carcinoma (HCC) and their therapeutic applications remain unclear. Differentially expressed lncRNA profile in HCC was constructed using TCGA data. LINC00958 expression level was examined in HCC cell lines and tissues. Univariate and multivariate analyses were performed to demonstrate the prognostic value of LINC00958. Loss-of-function and gain-of-function experiments were used to assess the effects of LINC00958 on cell proliferation, motility, and lipogenesis. Patient-derived xenograft model was established for in vivo experiments. RNA immunoprecipitation, dual luciferase reporter, biotin-labeled miRNA pull-down, fluorescence in situ hybridization, and RNA sequencing assays were performed to elucidate the underlying molecular mechanisms. We developed a PLGA-based nanoplatform encapsulating LINC00958 siRNA and evaluated its superiority for systemic administration. We identified a lipogenesis-related lncRNA, LINC00958, whose expression was upregulated in HCC cell lines and tissues. High LINC00958 level independently predicted poor overall survival. Functional assays showed that LINC00958 aggravated HCC malignant phenotypes in vitro and in vivo. Mechanistically, LINC00958 sponged miR-3619-5p to upregulate hepatoma-derived growth factor (HDGF) expression, thereby facilitating HCC lipogenesis and progression. METTL3-mediated N6-methyladenosine modification led to LINC00958 upregulation through stabilizing its RNA transcript. A PLGA-based nanoplatform loaded with si-LINC00958 was developed for HCC systemic administration. This novel drug delivery system was controlled release, tumor targeting, safe, and presented satisfactory antitumor efficacy. Our results delineate the clinical significance of LINC00958 in HCC and the regulatory mechanisms involved in HCC lipogenesis and progression, providing a novel prognostic indicator and promising nanotherapeutic target.
247 citations
TL;DR: It is indicated that AC020978 was upregulated in NSCLC, significantly correlated with advanced TNM stage and poor clinical outcomes, representing as an independent prognostic predictor and was a poor prognosticator.
Abstract: Rationale: Non-small cell lung cancer (NSCLC) is a deadly disease with a hallmark of aberrant metabolism. The mechanism of glycolysis associated lncRNA underlying the aggressive behaviors of NSCLC is poorly understood. Methods: The expression level of AC020978 in NSCLC was measured by quantitative real-time PCR and fluorescence in situ hybridization (FISH) assay. The biological role of AC020978 in cell proliferation and aerobic glycolysis was determined by functional experiments in vitro and in vivo. The transcription of AC020978 was assessed by dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assay. RNA pull-down, mass spectrometry and RNA immunoprecipitation (RIP) assays were used to identify the interaction protein with AC020978. Western blotting, in situ proximity ligation assay (PLA), and co-immunoprecipitation (co-IP) were performed to reveal the potential mechanism of AC020978. Results: The present study indicated that AC020978 was upregulated in NSCLC, significantly correlated with advanced TNM stage and poor clinical outcomes, representing as an independent prognostic predictor. Functional assays revealed AC020978's role in promoting cell growth and metabolic reprogramming. Moreover, AC020978 was an upregulated lncRNA under glucose starvation as well as hypoxia conditions, and directly transactivated by HIF-1α. Mechanistic investigations identified that AC020978 directly interacted with Pyruvate kinase isozymes M2 (PKM2) and enhanced PKM2 protein stability. Besides, this study uncovered that AC020978 could promote the nuclear translocation of PKM2 and regulate PKM2-enhanced HIF-1α transcription activity. Conclusions: Together, these data provided evidence that AC020978 conferred an aggressive phenotype to NSCLC and was a poor prognosticator. Targeting AC020978 might be an effective therapeutic strategy for NSCLC.
124 citations