LncRNAs: New Players in Apoptosis Control

Rossi, Marianna Nicoletta; Antonangeli, Fabrizio

doi:10.1155/2014/473857

Cited by 106 publications

(69 citation statements)

References 45 publications

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“…Notably, lncRNAs play an important role in dosage compensation, epigenetics, the cell cycle and differentiation (12). The primary functions of lncRNA include genomic imprinting, chromatin remodeling, mRNA transcriptional regulation and cell cycle regulation (13).…”

Section: Discussionmentioning

confidence: 99%

Unregulated long non-coding RNA-AK058003 promotes the proliferation, invasion and metastasis of breast cancer by regulating the expression levels of the γ-synuclein gene

Wang

2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the function of long chain non-coding RNA (lncRNA) in breast cancer cells. Quantitative polymerase chain reaction was used to measure mRNA expression levels in breast cancer tissues, adjacent tissues and in MCF-7 breast cancer cells. Western blot analysis was used to determine the protein expression levels. In addition, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was employed to measure the rates of cell proliferation. The invasion and migration of the MCF-7 cells were examined using a Transwell ® assay. The expression levels of lncRNA-AK058003 were increased significantly in the breast cancer tissues and were found to strongly correlate with the severity of the breast cancer clinical stage. Bioinformatics analysis revealed that the γ-synuclein gene (SNCG) may be a target gene regulated by lncRNA-AK058003. Thus, lncRNA-AK058803 was downregulated using small interfering RNA, and the mRNA and protein expression levels of SNCG were shown to be significantly reduced. Furthermore, the proliferation, invasion and migration rates of the MCF-7 breast cancer cells were significantly reduced. Therefore, the results demonstrated that unregulated lncRNA-AK058003 in breast cancer cells promotes cancer cell proliferation, invasion and metastasis via the regulation of SNCG expression. IntroductionBreast cancer is a common clinical condition with increasing morbidity and high mortality rates (1). Previous studies have suggested that the development of breast cancer is associated with inactivated tumor suppressor genes, dysfunctional signaling transduction pathways and other malfunctioning molecular signaling processes (2-4). With the development of chemotherapy, hormonal therapy, immunotherapy, gene therapy and other treatment technologies, the long-term survival of breast cancer patients has become possible. Breast cancer patients continue to succumb to the disease due to tumor metastasis, drug resistance and other reasons including hemorrhage, infection and recurrence (5). Therefore, finding novel biomarkers for use in the early diagnosis and treatment of breast cancer has become increasingly studied.A high-throughput sequencing study revealed the existence of types of non-coding RNA in gene transcripts, including small non-coding RNA and long non-coding (lnc)RNA (6). LncRNA has a length of >200 nucleotides and a similar structure to mRNA, including a 5' cap and poly-A tail. However, lncRNA is unable to encode proteins due to the absence of an open reading frame (7). Increasing numbers of studies have indicated that lncRNA may play an important role in various cellular processes, including cell differentiation, proliferation and apoptosis (8,9). Notably, a previous study revealed a novel function of lncRNA in the development of prostate cancer (10). In addition, long non-coding homeobox antisense intergenic RNA is reported to be a highly valuable clinical biomarker for the prognosis and early diagnosis of ovarian cancer (11).The primary functio...

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Section: Discussionmentioning

confidence: 99%

Unregulated long non-coding RNA-AK058003 promotes the proliferation, invasion and metastasis of breast cancer by regulating the expression levels of the γ-synuclein gene

Wang

2015

Experimental and Therapeutic Medicine

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“…Besides miRNAs, cancer cells often show altered expression patterns of diverse long noncoding RNAs (lncRNAs) in specific kinds of tumors when compared with normal cells and tissues. Therefore, their modulation (overexpression or down-regulation according to the specific lncRNA) in cancer cells often sensitizes cells to apoptotic treatments and consequently induces apoptosis, suggesting that targeting lncRNAs to modulate apoptosis in cancer cells can be utilized for cancer treatment (Rossi and Antonangeli, 2014).…”

Section: Role Of Apoptosis In Cancermentioning

confidence: 99%

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

Goldar¹,

Khaniani²,

Derakhshan³

et al. 2015

Asian Pacific Journal of Cancer Prevention

460

330

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Programmed cell death (PCD) or apoptosis is a mechanism which is crucial for all multicellular organisms to control cell proliferation and maintain tissue homeostasis as well as eliminate harmful or unnecessary cells from an organism. Defects in the physiological mechanisms of apoptosis may contribute to different human diseases like cancer. Identification of the mechanisms of apoptosis and its effector proteins as well as the genes responsible for apoptosis has provided a new opportunity to discover and develop novel agents that can increase the sensitivity of cancer cells to undergo apoptosis or reset their apoptotic threshold. These novel targeted therapies include those targeting anti-apoptotic Bcl-2 family members, p53, the extrinsic pathway, FLICE-inhibitory protein (c-FLIP), inhibitor of apoptosis (IAP) proteins, and the caspases. In recent years a number of these novel agents have been assessed in preclinical and clinical trials. In this review, we introduce some of the key regulatory molecules that control the apoptotic pathways, extrinsic and intrinsic death receptors, discuss how defects in apoptotic pathways contribute to cancer, and list several agents being developed to target apoptosis.

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“…Participation of lncRNA in chromosome maintenance, transcription regulation and mRNA and protein quality control mechanisms described above, as well as their newly defined roles in apoptosis and senescence, ensure their prominent effect on cancer development and treatment [reviewed in 72,87]. A large proportion of vlincRNAs serve as hallmarks of pluripotency and cancer [88].…”

Section: Therapeutic Aspects Of Lncrnasmentioning

confidence: 99%

Basic biology and therapeutic implications of lncRNA

Khorkova

Hsiao

Wahlestedt

2015

Advanced Drug Delivery Reviews

286

188

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Long non-coding RNAs (lncRNA), a class of non-coding RNA molecules recently identified largely due to the efforts of FANTOM, and later GENCODE and ENCODE consortia, have been a subject of intense investigation in the past decade. Extensive efforts to get deeper understanding of lncRNA biology have yielded evidence of their diverse structural and regulatory roles in protecting chromosome integrity, maintaining genomic architecture, X chromosome inactivation, imprinting, transcription, translation and epigenetic regulation. Here we wil briefly review the recent studies in the field of lncRNA biology focusing mostly on mammalian species and discuss their therapeutic implications.

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LncRNAs: New Players in Apoptosis Control

Cited by 106 publications

References 45 publications

Unregulated long non-coding RNA-AK058003 promotes the proliferation, invasion and metastasis of breast cancer by regulating the expression levels of the γ-synuclein gene

Unregulated long non-coding RNA-AK058003 promotes the proliferation, invasion and metastasis of breast cancer by regulating the expression levels of the γ-synuclein gene

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

Basic biology and therapeutic implications of lncRNA

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