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MiR-195 suppresses non-small cell lung cancer by targeting CHEK1.

Liu B, Qu J, Xu F, Guo Y, Wang Y, Yu H, Qian B - Oncotarget (2015)

Bottom Line: Our previous study showed high miR-195 plasma levels associated with favorable overall survival of non-smoking women with lung adenocarcinoma.We demonstrated that miR-195 expression was lower in tumor tissues and was associated with poor survival outcome.High expression of CHEK1 in lung tumors was associated with poor overall survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology and Biostatistics, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.

ABSTRACT
MiR-195 suppresses tumor growth and is associated with better survival outcomes in several malignancies including non-small cell lung cancer (NSCLC). Our previous study showed high miR-195 plasma levels associated with favorable overall survival of non-smoking women with lung adenocarcinoma. To further elucidate role of miR-195 in NSCLC, we conducted in vitro experiment as well as clinical studies in a cohort of 299 NSCLC samples. We demonstrated that miR-195 expression was lower in tumor tissues and was associated with poor survival outcome. Overexpression of miR-195 suppressed tumor cell growth, migration and invasion. We discovered that CHEK1 was a direct target of miR-195, which decreased CHEK1 expression in lung cancer cells. High expression of CHEK1 in lung tumors was associated with poor overall survival. Our results suggest that miR-195 suppresses NSCLC and predicts lung cancer prognosis.

No MeSH data available.


Related in: MedlinePlus

CHEK1 protein expression measured by immunehistochemical staining in tissue microarray and its association with lung cancer survival(A, B) Examples of NSCLC tissue samples stained with H&E or specific CHEK1 antibody under low (50×) and high (400×) power microscope; low CHEK1 expression was shown in panel A and high was in panel B (Scale bars represent 200 μm and 50 μm, respectively). (C) Kaplan–Meier overall survival curves according to low and high CHEK1 protein expression in 276 cases. Green line represents low protein expression, and red line represents high protein expression.
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Figure 5: CHEK1 protein expression measured by immunehistochemical staining in tissue microarray and its association with lung cancer survival(A, B) Examples of NSCLC tissue samples stained with H&E or specific CHEK1 antibody under low (50×) and high (400×) power microscope; low CHEK1 expression was shown in panel A and high was in panel B (Scale bars represent 200 μm and 50 μm, respectively). (C) Kaplan–Meier overall survival curves according to low and high CHEK1 protein expression in 276 cases. Green line represents low protein expression, and red line represents high protein expression.

Mentions: To assess if CHEK1 expression in NSCLC was associated with patient survival, we measured CHEK1 expression in 276 tumor samples with immunohistochemical staining (IHC). Results of representative tumor samples stained with high and low CHEK1 expression are shown in Figure 5A and 5B. CHEK1 expression was slightly higher in tumor than in adjacent non-tumor tissues, but the difference was not statistically significant (p = 0.832) (Data not shown). Compared to low expression, however, high CHEK1 expression was significantly associated with poor overall survival (p = 0.037) (Figure 5C). Cox regression analysis confirmed that CHEK1 was associated with survival after adjusting for confounding variables (HR, 1.42; 95% CI, 1.00–2.02) (Table 1). No statistically significant associations were found between CHEK1 expression and clinicopathological features of NSCLC (Supplementary Table 1).


MiR-195 suppresses non-small cell lung cancer by targeting CHEK1.

Liu B, Qu J, Xu F, Guo Y, Wang Y, Yu H, Qian B - Oncotarget (2015)

CHEK1 protein expression measured by immunehistochemical staining in tissue microarray and its association with lung cancer survival(A, B) Examples of NSCLC tissue samples stained with H&E or specific CHEK1 antibody under low (50×) and high (400×) power microscope; low CHEK1 expression was shown in panel A and high was in panel B (Scale bars represent 200 μm and 50 μm, respectively). (C) Kaplan–Meier overall survival curves according to low and high CHEK1 protein expression in 276 cases. Green line represents low protein expression, and red line represents high protein expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496229&req=5

Figure 5: CHEK1 protein expression measured by immunehistochemical staining in tissue microarray and its association with lung cancer survival(A, B) Examples of NSCLC tissue samples stained with H&E or specific CHEK1 antibody under low (50×) and high (400×) power microscope; low CHEK1 expression was shown in panel A and high was in panel B (Scale bars represent 200 μm and 50 μm, respectively). (C) Kaplan–Meier overall survival curves according to low and high CHEK1 protein expression in 276 cases. Green line represents low protein expression, and red line represents high protein expression.
Mentions: To assess if CHEK1 expression in NSCLC was associated with patient survival, we measured CHEK1 expression in 276 tumor samples with immunohistochemical staining (IHC). Results of representative tumor samples stained with high and low CHEK1 expression are shown in Figure 5A and 5B. CHEK1 expression was slightly higher in tumor than in adjacent non-tumor tissues, but the difference was not statistically significant (p = 0.832) (Data not shown). Compared to low expression, however, high CHEK1 expression was significantly associated with poor overall survival (p = 0.037) (Figure 5C). Cox regression analysis confirmed that CHEK1 was associated with survival after adjusting for confounding variables (HR, 1.42; 95% CI, 1.00–2.02) (Table 1). No statistically significant associations were found between CHEK1 expression and clinicopathological features of NSCLC (Supplementary Table 1).

Bottom Line: Our previous study showed high miR-195 plasma levels associated with favorable overall survival of non-smoking women with lung adenocarcinoma.We demonstrated that miR-195 expression was lower in tumor tissues and was associated with poor survival outcome.High expression of CHEK1 in lung tumors was associated with poor overall survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology and Biostatistics, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.

ABSTRACT
MiR-195 suppresses tumor growth and is associated with better survival outcomes in several malignancies including non-small cell lung cancer (NSCLC). Our previous study showed high miR-195 plasma levels associated with favorable overall survival of non-smoking women with lung adenocarcinoma. To further elucidate role of miR-195 in NSCLC, we conducted in vitro experiment as well as clinical studies in a cohort of 299 NSCLC samples. We demonstrated that miR-195 expression was lower in tumor tissues and was associated with poor survival outcome. Overexpression of miR-195 suppressed tumor cell growth, migration and invasion. We discovered that CHEK1 was a direct target of miR-195, which decreased CHEK1 expression in lung cancer cells. High expression of CHEK1 in lung tumors was associated with poor overall survival. Our results suggest that miR-195 suppresses NSCLC and predicts lung cancer prognosis.

No MeSH data available.


Related in: MedlinePlus