Pathologic effects of RNase-L dysregulation in immunity and proliferative control

Hassel, Bret A.

doi:10.2741/s298

Cited by 11 publications

(5 citation statements)

References 155 publications

(200 reference statements)

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“…Several studies have reported the antitumor effects of RNase L through several mechanisms, including the dependence on enzyme activity and regulations to specific signaling 3,14,37,38 . However, these studies mainly investigated the expression feature of RNase L and subsequent alteration of oncogenes that participated in cancer progression.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, by comparing lung cancer cells and normal pulmonary epithelial cells, we investigated the difference and altered phenotype that related to the function of RNase L between two kinds of cells and proposed the mechanism of how cancer cells impaired the function of RNase L. Another highlight of the present study is the function of RNase L in the nucleus. Previous studies focused on the function of RNase L in the cytoplasm that regulates signaling or molecules involved in cancer progression 3,14,38 . In our research, we found that RNase L was also located at the nucleus with high expression level both in lung epithelial cells and cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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IFN-γ restores the impaired function of RNase L and induces mitochondria-mediated apoptosis in lung cancer

et al. 2019

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RNase L is an essential component in interferon (IFN)-mediated antiviral signaling that showed antitumor effects in cancer. Cancer immunotherapy based on interferon has achieved encouraging results that indicate an applicable potential for cancer therapy. Here we showed that function of RNase L, though highly upregulated, was functionally impaired both in nuclear and cytoplasm in lung cancer cells. In normal lung epithelial cells, RNase L activation induced by 2–5A promoted nuclear condensation, DNA cleavage, and cell apoptosis, while in lung cancer cells, these processes were inhibited and RNase L-mediated downregulation of fibrillarin, Topo I and hnRNP A1 was also impaired in lung cancer cells. Moreover, the impairment of RNase L in lung cancer cells was due to the elevated expression of RLI. Application of IFN-γ to lung cancer cells led to enhanced expression of RNase L that compensated the RLI inhibition and restored the cytoplasmic and nuclear function of RNase L, leading to apoptosis of lung cancer cells. Thus, the present study discovered the impaired function and mechanism of RNase L in lung cancer cells and proved the efficacy of IFN-γ in restoring RNase L function and inducing apoptosis in the lung cancer cell. These results indicated the RNase L as a therapeutic target in lung cancer cells and immunotherapy of IFN-γ may serve as an adjuvant to enhance the efficacy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

IFN-γ restores the impaired function of RNase L and induces mitochondria-mediated apoptosis in lung cancer

et al. 2019

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“…(65–67) RNASEL variants have been associated with elevated inflammatory biomarkers(68) and the enzyme encoded by the RNASEL gene has proinflammatory functions. (69)…”

Section: Discussionmentioning

confidence: 99%

Family History of Cancer in Relation to Breast Cancer Subtypes in African American Women

Bethea

Rosenberg

Castro‐Webb

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Evidence on the relation of family history of cancers other than breast cancer to breast cancer risk is conflicting and most studies have not assessed specific breast cancer subtypes. Methods We assessed the relation of first degree family history of breast, prostate, lung, colorectal, ovarian, cervical cancer, and lymphoma or leukemia, to risk of estrogen receptor positive (ER+), ER−, and triple negative breast cancer in data from the African American Breast Cancer Epidemiology and Risk Consortium. Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results There were 3,023 ER+ and 1,497 ER− breast cancer cases (including 696 triple negative cases) and 17,420 controls. First degree family history of breast cancer was associated with increased risk of each subtype: OR=1.76 (95% CI 1.57–1.97) for ER+, 1.67 (1.42–1.95) for ER−, and 1.72 (1.38–2.13) for triple negative breast cancer. Family history of cervical cancer was associated with increased risk of ER− (OR=2.39, 95% CI 1.36–4.20), but not ER+ cancer. Family history of both breast and prostate cancer was associated with increased risk of ER+ (3.40, 2.42–4.79) and ER− (2.09, 1.21–3.63) cancer, but family history of both breast and lung cancer was associated only with ER− cancer (2.11, 1.29–3.46). Conclusions A family history of cancers other than breast may influence risk of breast cancer and associations may differ by subtype. Impact Greater surveillance and counseling for additional screening may be warranted for women with a family history of cancer.

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“…RNASEL plays a significant role in viral clearance and it has been suggested that variation in RNASEL may alter risk of viral-associated cancers, such as head and neck squamous cell carcinoma and cervical cancer, as well as non-viral cancers such as breast cancer [45], [46]. Discrepancies between large studies of hereditary prostate cancer suggest that environmental factors, such as viral infection, may modulate the impact of RNASEL variation on carcinogenesis [18].…”

Section: Discussionmentioning

confidence: 99%

RNASEL and MIR146A SNP-SNP Interaction as a Susceptibility Factor for Non-Melanoma Skin Cancer

et al. 2014

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Immunity and inflammatory pathways are important in the genesis of non-melanoma skin cancers (NMSC). Functional genetic variation in immune modulators has the potential to affect disease etiology. We investigated associations between common variants in two key regulators, MIR146A and RNASEL, and their relation to NMSCs. Using a large population-based case-control study of basal cell (BCC) and squamous cell carcinoma (SCC), we investigated the impact of MIR146A SNP rs2910164 on cancer risk, and interaction with a SNP in one of its putative targets (RNASEL, rs486907). To examine associations between genotype and BCC and SCC, occurrence odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using unconditional logistic regression, accounting for multiple confounding factors. We did not observe an overall change in the odds ratios for SCC or BCC among individuals carrying either of the RNASEL or MIR146A variants compared with those who were wild type at these loci. However, there was a sex-specific association between BCC and MIR146A in women (ORGC = 0.73, [95%CI = 0.52–1.03]; ORCC = 0.29, [95% CI = 0.14–0.61], p-trend<0.001), and a reduction in risk, albeit not statistically significant, associated with RNASEL and SCC in men (ORAG = 0.88, [95%CI = 0.65–1.19]; ORAA = 0.68, [95%CI = 0.43–1.08], p-trend = 0.10). Most striking was the strong interaction between the two genes. Among individuals carrying variant alleles of both rs2910164 and rs486907, we observed inverse relationships with SCC (ORSCC = 0.56, [95%CI = 0.38–0.81], p-interaction = 0.012) and BCC (ORBCC = 0.57, [95%CI = 0.40–0.80], p-interaction = 0.005). Our results suggest that genetic variation in immune and inflammatory regulators may influence susceptibility to NMSC, and novel SNP-SNP interaction for a microRNA and its target. These data suggest that RNASEL, an enzyme involved in RNA turnover, is controlled by miR-146a and may be important in NMSC etiology.

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Pathologic effects of RNase-L dysregulation in immunity and proliferative control

Cited by 11 publications

References 155 publications

IFN-γ restores the impaired function of RNase L and induces mitochondria-mediated apoptosis in lung cancer

IFN-γ restores the impaired function of RNase L and induces mitochondria-mediated apoptosis in lung cancer

Family History of Cancer in Relation to Breast Cancer Subtypes in African American Women

RNASEL and MIR146A SNP-SNP Interaction as a Susceptibility Factor for Non-Melanoma Skin Cancer

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