Low-level expression of let-7a in gastric cancer and its involvement in tumorigenesis by targeting RAB40C

Qiaoyuan Yang; Zhigang Jie; Hong Cao; Anne R. Greenlee; Chengfeng Yang; Fei Zou; Yiguo Jiang

doi:10.1093/carcin/bgr035

Low-level expression of let-7a in gastric cancer and its involvement in tumorigenesis by targeting RAB40C

Qiaoyuan Yang, Zhigang Jie, Hong Cao, Anne R. Greenlee, Chengfeng Yang, Fei Zou, Yiguo Jiang

Markey Cancer Center / Cancer Research Priority Initiative

Research output: Contribution to journal › Article › peer-review

99 Scopus citations

Abstract

Gastric cancer is the fourth most common cancer and the second leading cause of cancer mortality worldwide but the underlying molecular mechanism is not entirely clear. The objective of this study was to explore the role of let-7a microRNA (miRNA) in gastric tumorigenesis and the possible correlation between RAB40C and let-7a miRNA in gastric cancer. We found that expression of let-7a is reduced in human gastric cancer tissues and cell lines and there was a significant correlation between the level of let-7a expression and the stage of differentiation. Overexpression of let-7a resulted in a decrease in cell proliferation and G1 arrest, significantly suppressed anchorage-dependent growth in vitro and the tumorigenicity of gastric cancer cells in a nude mouse xenograft model. Furthermore, we demonstrated that RAB40C is regulated directly by let-7a and plays an essential role as a mediator of the biological effects of let-7a in gastric tumorigenesis. This study revealed that let-7a is significant in suppressing gastric cancer growth in vivo and in vitro and provided the first evidence that RAB40C is negatively regulated by let-7a at the posttranscriptional level via binding to the 3#-untranslated region of RAB40C messenger RNA in gastric cancer. The results of this study suggest that let-7a and RAB40C are potentially useful targets for gastric cancer diagnosis and therapy.

Original language	English
Pages (from-to)	713-722
Number of pages	10
Journal	Carcinogenesis
Volume	32
Issue number	5
DOIs	https://doi.org/10.1093/carcin/bgr035
State	Published - May 2011

Bibliographical note

Funding Information:
National Natural Science Foundation of China (30771780, 30972443 to J.Y.); Natural Science Foundation of Guangdong Province (07117550, 9251018201000004 to J.Y.); Science and Technology Program of Guangzhou Bureau of Education (08A093 to J.Y., 08A092 to Y.Q.); Science and Technology Pillar Program of Jiangxi Province (2009zDS16000 to C.H.).

Funding

National Natural Science Foundation of China (30771780, 30972443 to J.Y.); Natural Science Foundation of Guangdong Province (07117550, 9251018201000004 to J.Y.); Science and Technology Program of Guangzhou Bureau of Education (08A093 to J.Y., 08A092 to Y.Q.); Science and Technology Pillar Program of Jiangxi Province (2009zDS16000 to C.H.).

Funders	Funder number
Science and Technology Pillar Program of Jiangxi Province	2009zDS16000
Science and Technology Program of Guangzhou Bureau of Education	08A092, 08A093
National Natural Science Foundation of China (NSFC)	30771780, 30972443
National Natural Science Foundation of China (NSFC)
Natural Science Foundation of Guangdong Province	9251018201000004, 07117550
Natural Science Foundation of Guangdong Province

ASJC Scopus subject areas

Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/carcin/bgr035

Cite this

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title = "Low-level expression of let-7a in gastric cancer and its involvement in tumorigenesis by targeting RAB40C",

abstract = "Gastric cancer is the fourth most common cancer and the second leading cause of cancer mortality worldwide but the underlying molecular mechanism is not entirely clear. The objective of this study was to explore the role of let-7a microRNA (miRNA) in gastric tumorigenesis and the possible correlation between RAB40C and let-7a miRNA in gastric cancer. We found that expression of let-7a is reduced in human gastric cancer tissues and cell lines and there was a significant correlation between the level of let-7a expression and the stage of differentiation. Overexpression of let-7a resulted in a decrease in cell proliferation and G1 arrest, significantly suppressed anchorage-dependent growth in vitro and the tumorigenicity of gastric cancer cells in a nude mouse xenograft model. Furthermore, we demonstrated that RAB40C is regulated directly by let-7a and plays an essential role as a mediator of the biological effects of let-7a in gastric tumorigenesis. This study revealed that let-7a is significant in suppressing gastric cancer growth in vivo and in vitro and provided the first evidence that RAB40C is negatively regulated by let-7a at the posttranscriptional level via binding to the 3#-untranslated region of RAB40C messenger RNA in gastric cancer. The results of this study suggest that let-7a and RAB40C are potentially useful targets for gastric cancer diagnosis and therapy.",

author = "Qiaoyuan Yang and Zhigang Jie and Hong Cao and Greenlee, {Anne R.} and Chengfeng Yang and Fei Zou and Yiguo Jiang",

note = "Funding Information: National Natural Science Foundation of China (30771780, 30972443 to J.Y.); Natural Science Foundation of Guangdong Province (07117550, 9251018201000004 to J.Y.); Science and Technology Program of Guangzhou Bureau of Education (08A093 to J.Y., 08A092 to Y.Q.); Science and Technology Pillar Program of Jiangxi Province (2009zDS16000 to C.H.).",

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AU - Yang, Qiaoyuan

AU - Jie, Zhigang

AU - Cao, Hong

AU - Greenlee, Anne R.

AU - Yang, Chengfeng

AU - Zou, Fei

AU - Jiang, Yiguo

N1 - Funding Information: National Natural Science Foundation of China (30771780, 30972443 to J.Y.); Natural Science Foundation of Guangdong Province (07117550, 9251018201000004 to J.Y.); Science and Technology Program of Guangzhou Bureau of Education (08A093 to J.Y., 08A092 to Y.Q.); Science and Technology Pillar Program of Jiangxi Province (2009zDS16000 to C.H.).

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N2 - Gastric cancer is the fourth most common cancer and the second leading cause of cancer mortality worldwide but the underlying molecular mechanism is not entirely clear. The objective of this study was to explore the role of let-7a microRNA (miRNA) in gastric tumorigenesis and the possible correlation between RAB40C and let-7a miRNA in gastric cancer. We found that expression of let-7a is reduced in human gastric cancer tissues and cell lines and there was a significant correlation between the level of let-7a expression and the stage of differentiation. Overexpression of let-7a resulted in a decrease in cell proliferation and G1 arrest, significantly suppressed anchorage-dependent growth in vitro and the tumorigenicity of gastric cancer cells in a nude mouse xenograft model. Furthermore, we demonstrated that RAB40C is regulated directly by let-7a and plays an essential role as a mediator of the biological effects of let-7a in gastric tumorigenesis. This study revealed that let-7a is significant in suppressing gastric cancer growth in vivo and in vitro and provided the first evidence that RAB40C is negatively regulated by let-7a at the posttranscriptional level via binding to the 3#-untranslated region of RAB40C messenger RNA in gastric cancer. The results of this study suggest that let-7a and RAB40C are potentially useful targets for gastric cancer diagnosis and therapy.

AB - Gastric cancer is the fourth most common cancer and the second leading cause of cancer mortality worldwide but the underlying molecular mechanism is not entirely clear. The objective of this study was to explore the role of let-7a microRNA (miRNA) in gastric tumorigenesis and the possible correlation between RAB40C and let-7a miRNA in gastric cancer. We found that expression of let-7a is reduced in human gastric cancer tissues and cell lines and there was a significant correlation between the level of let-7a expression and the stage of differentiation. Overexpression of let-7a resulted in a decrease in cell proliferation and G1 arrest, significantly suppressed anchorage-dependent growth in vitro and the tumorigenicity of gastric cancer cells in a nude mouse xenograft model. Furthermore, we demonstrated that RAB40C is regulated directly by let-7a and plays an essential role as a mediator of the biological effects of let-7a in gastric tumorigenesis. This study revealed that let-7a is significant in suppressing gastric cancer growth in vivo and in vitro and provided the first evidence that RAB40C is negatively regulated by let-7a at the posttranscriptional level via binding to the 3#-untranslated region of RAB40C messenger RNA in gastric cancer. The results of this study suggest that let-7a and RAB40C are potentially useful targets for gastric cancer diagnosis and therapy.

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Low-level expression of let-7a in gastric cancer and its involvement in tumorigenesis by targeting RAB40C

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

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