Expression of miR-34a-5p is up-regulated in human colorectal cancer and correlates with survival and clock gene PER2 expression

Hasakova, Kristina; Reis, Richard M.; Vician, M; Zeman, Michal; Herichová, Iveta

doi:10.1371/journal.pone.0224396

Cited by 45 publications

(48 citation statements)

References 55 publications

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“…miR-34a is downregulated in different cancers, including breast cancer, lung cancer, bladder cancer, and pancreatic cancer (5,42,43). We analyzed the expression of miR-34a in TCGA tumor samples.…”

Section: Resultsmentioning

confidence: 99%

“…miR-34a is encoded by its own transcript, while miR-34b and miR-34c share a common transcript and are dysregulated in some cancers (3). Decreased levels of miR-34a expression have been reported in and linked to the pathogenesis of numerous types of cancer, including ovarian cancer, colorectal cancer, pediatric neuroblastoma, hepatocellular carcinoma, triple-negative breast cancer, lung adenocarcinomas, bladder cancer, prostate cancer, and osteosarcoma (4)(5)(6)(7)(8)(9)(10)(11)(12). The locus harboring the miR-34a transcripts is in a region associated with a genomic fragile site on chromosome 1p.…”

Section: Introductionmentioning

confidence: 99%

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Down-regulation of tumor suppressor miR-34a contributes to head and neck cancer by up-regulating MET oncogene and modulating tumor immune evasion

Cheng

Mathew

et al. 2020

Preprint

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Background: MicroRNAs (miRs) have been shown to play an important role in tumorigenesis, including in head and neck squamous cell carcinoma (HNSCC). The miR-34a family is thought to play a role in tumor suppression, but the exact mechanism of action in HNSCC is not well understood. In addition, miR-34a is generally down-regulated HNSCC, but the role of chromosomal changes and mutation status on miR-34a expression remain unknown. Methods: Differential expression of miR-34a-3p, MET, and genomic alterations were assessed in the Cancer Genome Atlas (TCGA) datasets as well as primary HNSCC and adjacent normal tissue. The biological functions of miR-34a in HNSCC were investigated in samples derived from primary human tumors. The expression of MET was evaluated using immunohistochemistry, and the molecular interaction of miR-34a and MET were demonstrated by RNA pulldown, RNA immunoprecipitation, and rescue experiments. Lastly, mouse xenograft and locked nucleic acid anti-miRs were used to evaluate the clinical relevance of miR-34a in HNSCC tumor growth and modulation of the tumor microenvironment in vivo.Results: Chromosome arm 1p loss and P53 mutations are both associated with lower levels of miR-34a. In HNSCC, miR-34a acts as a tumor suppressor and physically interacts with and functionally targets the proto-oncogene MET. We found that miR-34a suppresses HNSCC carcinogenesis, at least in part, by downregulating MET, consequently inhibiting HNSCC proliferation. Moreover, ectopic expression of miR-34a reduces HNSCC cell proliferation and tumor burden in vitro and in vivo, represses expression of genes involved in epithelial-mesenchymal transition, and negates the oncogenic effect of MET in mouse tumors. In HNSCC patient samples, higher levels of miR-34a are significantly associated with a higher frequency of Th1 cells, myeloid cells, and regulatory T cells. Consistent with these findings, inhibition of miR-34a in an in vivo model of HNSCC leads to an increased number of immunosuppressive PDL1-expressing tumor-associated macrophages in the tumor microenvironment. Conclusions: Our results demonstrate that miR-34a directly targets MET and maintains anti-tumor immune activity, and could potentially represent a new therapeutic approach for HNSCC.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Down-regulation of tumor suppressor miR-34a contributes to head and neck cancer by up-regulating MET oncogene and modulating tumor immune evasion

Cheng

Mathew

et al. 2020

Preprint

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“…Several lines of recent evidence show that clock components are also regulated by miRNAs. The Period genes, Per1, Per2 and Per3, which are regulated in mammals by common miRNAs, such as miR-24, miR-29 family members (miR-29a, miR-29b and miR-29c), miR-30a, miR-34a-5p, miR-192 and miR-194, are likely to be involved in the timekeeping mechanism in most tissues, given that they are widely expressed in several types of cells or tissues [21,[24][25][26][27]. Further, Per2 is likely to be regulated by miR-449a, which also targeted PPP1, a dephosphorylation enzyme of PER2 phosphorylation by CKIε according to the computational analysis of microarray data using the SCN of Clock-mutant mice [30].…”

Section: Interplay Of Circadian Genes and Mirnasmentioning

confidence: 99%

MicroRNA: A Key Player for the Interplay of Circadian Rhythm Abnormalities, Sleep Disorders and Neurodegenerative Diseases

et al. 2020

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Circadian rhythms are endogenous 24-h oscillators that regulate the sleep/wake cycles and the timing of biological systems to optimize physiology and behavior for the environmental day/night cycles. The systems are basically generated by transcription–translation feedback loops combined with post-transcriptional and post-translational modification. Recently, evidence is emerging that additional non-coding RNA-based mechanisms are also required to maintain proper clock function. MicroRNA is an especially important factor that plays critical roles in regulating circadian rhythm as well as many other physiological functions. Circadian misalignment not only disturbs the sleep/wake cycle and rhythmic physiological activity but also contributes to the development of various diseases, such as sleep disorders and neurodegenerative diseases. The patient with neurodegenerative diseases often experiences profound disruptions in their circadian rhythms and/or sleep/wake cycles. In addition, a growing body of recent evidence implicates sleep disorders as an early symptom of neurodegenerative diseases, and also suggests that abnormalities in the circadian system lead to the onset and expression of neurodegenerative diseases. The genetic mutations which cause the pathogenesis of familial neurodegenerative diseases have been well studied; however, with the exception of Huntington’s disease, the majority of neurodegenerative diseases are sporadic. Interestingly, the dysfunction of microRNA is increasingly recognized as a cause of sporadic neurodegenerative diseases through the deregulated genes related to the pathogenesis of neurodegenerative disease, some of which are the causative genes of familial neurodegenerative diseases. Here we review the interplay of circadian rhythm disruption, sleep disorders and neurodegenerative disease, and its relation to microRNA, a key regulator of cellular processes.

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“…3 -UTR of all PER genes contain putative target sites for miR-192/miR-194. The miR-34a-5p targets CRY1, PER1 and PER2) of molecular clockwork [59,[73][74][75]. Likewise, miR-24 and miR-29b have been shown to directly suppress PER2 and PER3, respectively [59,76].…”

Section: Role Of Micrornas In Molecular Clock Regulation: Implicationmentioning

confidence: 99%

Role of Non-Coding RNAs in Lung Circadian Clock Related Diseases

Chinnapaiyan

Dutta

Devadoss

et al. 2020

IJMS

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Circadian oscillations are regulated at both central and peripheral levels to maintain physiological homeostasis. The central circadian clock consists of a central pacemaker in the suprachiasmatic nucleus that is entrained by light dark cycles and this, in turn, synchronizes the peripheral clock inherent in other organs. Circadian dysregulation has been attributed to dysregulation of peripheral clock and also associated with several diseases. Components of the molecular clock are disrupted in lung diseases like chronic obstructive pulmonary disease (COPD), asthma and IPF. Airway epithelial cells play an important role in temporally organizing magnitude of immune response, DNA damage response and acute airway inflammation. Non-coding RNAs play an important role in regulation of molecular clock and in turn are also regulated by clock components. Dysregulation of these non-coding RNAs have been shown to impact the expression of core clock genes as well as clock output genes in many organs. However, no studies have currently looked at the potential impact of these non-coding RNAs on lung molecular clock. This review focuses on the ways how these non-coding RNAs regulate and in turn are regulated by the lung molecular clock and its potential impact on lung diseases.

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Expression of miR-34a-5p is up-regulated in human colorectal cancer and correlates with survival and clock gene PER2 expression

Cited by 45 publications

References 55 publications

Down-regulation of tumor suppressor miR-34a contributes to head and neck cancer by up-regulating MET oncogene and modulating tumor immune evasion

Down-regulation of tumor suppressor miR-34a contributes to head and neck cancer by up-regulating MET oncogene and modulating tumor immune evasion

MicroRNA: A Key Player for the Interplay of Circadian Rhythm Abnormalities, Sleep Disorders and Neurodegenerative Diseases

Role of Non-Coding RNAs in Lung Circadian Clock Related Diseases

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