Altered patterns of expression of members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family in lung cancer

Pino, Irene; Pı́o, Rubén; Toledo, Gemma; Zabalegui, Natalia; Vicent, Silvestre; Rey, Nolwen L.; Lozano, Marı́a D.; Torre, W.; Garcı́a-Foncillas, Jesús; Montuenga, Luis M.

doi:10.1016/s0169-5002(03)00193-4

Cited by 144 publications

(129 citation statements)

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“…Elevated expression of HNRNPC has been observed in multiple types of tumors and tumor cells (Pino et al , 2003; Sun et al , 2007; Park et al , 2012; Mulnix et al , 2014). The present study was focused on the potential function of HNRNPC in breast cancer cells.…”

Section: Resultsmentioning

confidence: 99%

“…Aberrant up‐regulation of heterogeneous nuclear ribonucleoprotein C (HNRNPC) has been observed in multiple tumors or tumor cell lines, including glioblastoma (Park et al , 2012), hepatocellular carcinoma (Sun et al , 2007), melanoma (Mulnix et al , 2014), and lung cancer (Pino et al , 2003). As an RNA binding protein (RBP), HNRNPC is well known for its regulatory roles in RNA splicing (Konig et al , 2010; Zarnack et al , 2013), sequence‐unspecific RNA exportation (McCloskey et al , 2012), RNA expression (Christian et al , 2008; Park et al , 2012), stability (Shetty, 2005; Velusamy et al , 2008), 3′ end processing (Gruber et al , 2016), and translation (Kim et al , 2003; Meng et al , 2008; Spahn et al , 2008; Lee et al , 2010).…”

Section: Introductionmentioning

confidence: 99%

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Function of HNRNPC in breast cancer cells by controlling the dsRNA‐induced interferon response

et al. 2018

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Elevated expression of RNA binding protein HNRNPC has been reported in cancer cells, while the essentialness and functions of HNRNPC in tumors were not clear. We showed that repression of HNRNPC in the breast cancer cells MCF7 and T47D inhibited cell proliferation and tumor growth. Our computational inference of the key pathways and extensive experimental investigations revealed that the cascade of interferon responses mediated by RIG‐I was responsible for such tumor‐inhibitory effect. Interestingly, repression of HNRNPC resulted in accumulation of endogenous double‐stranded RNA (dsRNA), the binding ligand of RIG‐I. These up‐regulated dsRNA species were highly enriched by Alu sequences and mostly originated from pre‐mRNA introns that harbor the known HNRNPC binding sites. Such source of dsRNA is different than the recently well‐characterized endogenous retroviruses that encode dsRNA. In summary, essentialness of HNRNPC in the breast cancer cells was attributed to its function in controlling the endogenous dsRNA and the down‐stream interferon response. This is a novel extension from the previous understandings about HNRNPC in binding with introns and regulating RNA splicing.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Function of HNRNPC in breast cancer cells by controlling the dsRNA‐induced interferon response

et al. 2018

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“…The expression of hnRNP K is aberrantly increased in numerous cancers, including nasopharyngeal carcinoma (NPC; Pino et al, 2003;Carpenter et al, 2006;Hatakeyama et al, 2006;Roychoudhury and Chaudhuri, 2007;Chen et al, 2008). The tumorigenic activity of hnRNP K is conferred through its ability to increase proliferation (Lynch et al, 2005), clonogenic potential (Notari et al, 2006) and metastasis (Inoue et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Thymidine phosphorylase mRNA stability and protein levels are increased through ERK-mediated cytoplasmic accumulation of hnRNP K in nasopharyngeal carcinoma cells

Liu

et al. 2009

Oncogene

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The cytoplasmic level of heterogeneous nuclear ribonucleoprotein K (hnRNP K) is significantly correlated with the elevated expression of thymidine phosphorylase (TP), and high levels of both proteins are predictive of a poor prognosis in nasopharyngeal carcinoma (NPC). We herein show that TP is highly induced by serum deprivation in NPC cells, and that this is due to an increase in the halflife of the TP mRNA, as shown by nuclear run-on and actinomycin D assays. We further show that the CU-rich element of the TP mRNA directly interacts with hnRNP K, as demonstrated by immunoprecipitation RT-PCR assays, and the nucleus-to-cytoplasm translocation of hnRNP K. Blockade of hnRNP K expression reduces TP expression, suggesting that hnRNP K acts in the upregulation of TP. Mechanistically, both MEK inhibitor and the hnRNP K ERK-phosphoacceptor-site mutant decrease cytoplasmic accumulation of hnRNP K, suggesting that ERK-dependent phosphorylation is critical for TP induction. Furthermore, we found that hnRNP Kmediated TP induction allows NPC cells to resist hypoxia-induced apoptosis. Our results collectively establish the regulation and role of ERK-mediated cytoplasmic accumulation of hnRNP K as an upstream modulator of TP, suggesting that hnRNP K may be an attractive candidate as a future therapeutic target for cancer.

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“…In breast cancer cells, overexpression of hnRNP K enhances cell proliferation and anchorage-independent growth (Mandal et al, 2001), and in several states of enhanced cell proliferation, increased expression of this protein has also been found . Overexpression of hnRNP K has been shown in many human tumours too, including lung cancer (Pino et al, 2003), esophageal cancer (Hatakeyama et al, 2006), oral squamous cell carcinoma (Roychoudhury and Chaudhuri, 2007), colorectal cancer (Carpenter et al, 2006b) and nasopharyngeal carcinoma (Chen et al, 2008). Interestingly, in the latter three both aberrant hnRNP K localisation and a correlation between protein expression and patient's prognosis were also observed.…”

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confidence: 98%

Heterogeneous nuclear ribonucleoprotein K: altered pattern of expression associated with diagnosis and prognosis of prostate cancer

et al. 2009

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Using proteomic analysis of the nuclear matrix (NM), we found that heterogeneous nuclear ribonucleoprotein K (hnRNP K), a member of the hnRNP family with pleiotropic functions, was differentially expressed in prostate cancer (PCa) tissues. This study aimed to characterise the expression of hnRNP K and its subcellular localisation in PCa, utilising immunohistochemical and quantitative western blot techniques. Furthermore, the hnRNP K expression was studied in human PCa cell lines in order to determine its modulation by bicalutamide, the anti-androgen widely used in PCa therapy. Immunohistochemical staining of paraffinembedded tissues showed that hnRNP K was overexpressed in PCa, where it was localised both in the cytoplasm and in the nucleus. Staining of non-tumour tissues showed exclusively nuclear localisation and a less intense or absent signal. Immunoblot analysis demonstrated that the hnRNP K level within the NM was higher in PCa compared with non-tumour tissues and closely correlated with Gleason score (P ¼ 0.008). Higher expression within the NM was significantly (P ¼ 0.032) associated with poor prognosis. In two-dimensional western blot analysis hnRNP K presented several isoforms; the one with pI 5.1 was the most differently expressed between non-tumour and PCa tissues. Preliminary results indicate that hnRNP K can be modulated in vitro by a non-steroidal antiandrogen. Taken together, our findings suggest that hnRNP K has potential implications at the diagnostic, prognostic and therapeutic levels in PCa.

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Altered patterns of expression of members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family in lung cancer

Cited by 144 publications

References 50 publications

Function of HNRNPC in breast cancer cells by controlling the dsRNA‐induced interferon response

Function of HNRNPC in breast cancer cells by controlling the dsRNA‐induced interferon response

Thymidine phosphorylase mRNA stability and protein levels are increased through ERK-mediated cytoplasmic accumulation of hnRNP K in nasopharyngeal carcinoma cells

Heterogeneous nuclear ribonucleoprotein K: altered pattern of expression associated with diagnosis and prognosis of prostate cancer

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