METTL3 promote tumor proliferation of bladder cancer by accelerating pri-miR221/222 maturation in m6A-dependent manner
By Jie Han, Jing-zi Wang, Xiao Yang, Hao Yu, R. Zhou, Hongcheng Lu, Wenbo Yuan, Jiancheng Lu, Zi-jian Zhou, Q. Lu and 2 more. Molecular Cancer, 2019
611 citations recorded by the source corpus.
METTL3 is known to be involved in all stages in the life cycle of RNA. It affects the tumor formation by the regulation the m6A modification in the mRNAs of critical oncogenes or tumor suppressors. In bladder cancer, METTL3 could promote the bladder cancer progression via AFF4/NF-κB/MYC signaling network by an m6A dependent manner. Recently, METTL3 was also found to affect the m6A modification in non-coding RNAs including miRNAs, lincRNAs and circRNAs. However, whether this mechanism is related to the proliferation of tumors induced by METTL3 is not reported yet. Quantitative real-time PCR, western blot and immunohistochemistry were used to detect the expression of METTL3 in bladder cancer. The survival analysis was adopted to explore the association between METTL3 expression and the prognosis of bladder cancer. Bladder cancer cells were stably transfected with lentivirus and cell proliferation and cell cycle, as well as tumorigenesis in nude mice were performed to assess the effect of METTL3 in bladder cancer. RNA immunoprecipitation (RIP), co-immunoprecipitations and RNA m6A dot blot assays were conducted to confirm that METTL3 interacted with the microprocessor protein DGCR8 and modulated the pri-miR221/222 process in an m6A-dependent manner. Luciferase reporter assay was employed to identify the direct binding sites of miR221/222 with PTEN. Colony formation assay and CCK8 assays were conducted to confirm the function of miR-221/222 in METTL3-induced cell growth in bladder cancer. We confirmed the oncogenic role of METTL3 in bladder cancer by accelerating the maturation of pri-miR221/222, resulting in the reduction of PTEN, which ultimately leads to the proliferation of bladder cancer. Moreover, we found that METTL3 was significantly increased in bladder cancer and correlated with poor prognosis of bladder cancer patients. Our findings suggested that METTL3 may have an oncogenic role in bladder cancer through interacting with the microprocessor protein DGCR8 and positively modulating the pri-miR221/222 process in an m6A-dependent manner. To our knowledge, this is the first comprehensive study that METTL3 affected the tumor formation by the regulation the m6A modification in non-coding RNAs, which might provide fresh insights into bladder cancer therapy.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/1107bea92d10eead54fd25db8de32d0d93d87a6d
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cancer Research
In Molecular Biology
Citations in the corpus
- Functions of N6-methyladenosine and its role in cancer (2019, neutral): “METTL3 promotes maturation of primiR221/222 [130].”
- The potential role of RNA N6-methyladenosine in Cancer progression (2020, background): “This study confirmed the carcinogenic role of METTL3 in bladder cancer [129].”
- The role of m6A RNA methylation in cancer metabolism (2022, background): “METTL3 is significantly increased in bladder cancer, which can interaction with DGCR8 promotes the maturation of pri-miR-221/222 family in an m6A dependent manner, reduces the expression of downstream gene PTEN through synergistic effect, and promotes the progression of bladder cancer and poor progn”