The Association of microRNA-34a With High Incidence and Metastasis of Lung Cancer in Gejiu and Xuanwei Yunnan

Abstract

The incidence and associated mortality of lung cancer in tin miners in Gejiu County and farmers in Xuanwei Country, Yunnan Province have been very high in the world. Current published literatures on the molecular mechanisms of lung cancer initiation and progression in Gejiu and Xuanwei County are still controversial. Studies confirmed that microRNA-34a (miR-34a) functioned as a vital tumor suppressor in tumorigenesis and progression. However, the role and precise mechanisms of miR-34a and its regulatory gene network in initiation and progression of lung cancer in Gejiu and Xuanwei County, Yunnan Province, have not been elucidated. In the current study, we first found that miR-34a was downregulated in Gejiu lung squamous carcinoma YTMLC-90, Xuanwei lung adenocarcinoma XWLC-05, and other non-small cell lung carcinoma (NSCLC) cell lines, and miR-34a overexpression inhibited cell proliferation, migration and invasion, as well as induced cell apoptosis in YTMLC-90 and XWLC-05 cells. Our findings revealed that miR-34a is critical and cannot be considered as the area-specific non-coding RNA in initiation and progression of lung cancer in Gejiu and Xuanwei County. Next we revealed that miR-34a overexpression suppressed lung cancer growth and metastasis partially via increasing PTEN but reducing CDK6 expression that might lead to subsequent inactivation of PI3K/AKT pathway. Furthermore, our findings demonstrated that YY1 functioned as a tumor suppressor gene in initiation and progression of lung cancer in Gejiu and Xuanwei County. In conclusion, our findings in the study confirmed that miR-34a overexpression could simultaneously suppress tumor growth and metastasis and play a vital role in tumorigenesis and progression of NSCLC via increasing PTEN and YY1 expression, but decreasing CDK6. Most interestingly, our findings also raised doubts about the current ideas about these area-specific diseases.

Regulation of apoptosis, autophagy and ferroptosis by non‑coding RNAs in metastatic non‑small cell lung cancer (Review)

“…In addition, miR-139-5p may also induce apoptosis in NSCLC cells by targeting and regulating YAF1 via the AKT/p38 MAPK signaling pathway ( 64 ). The overexpression of miR-34a has been shown to inhibit NSCLC growth and metastasis by increasing PTEN and decreasing CDK6 expression levels, as reported in tin miners in Gejiu County and farmers in Xuanwei ( 65 ). miR-30a may sensitize NSCLC cells by promoting DDP/pemetrexed-induced apoptosis and by enhancing autophagy in NSCLC cells ( 60 ).…”

Advances in the role of microRNAs associated with the PI3K/AKT signaling pathway in lung cancer

“…For example, miR-126 expression was markedly downregulated in NSCLC,miR-126 overexpression, which targets PIK3R2 and deactivates the PI3K-Akt signaling pathway, inhibits LUAD cell proliferation as well as tumor growth rate and size in xenograft tumor models ( 47 ) ( 87 )ADDIN.By obstructing the PI3K/Akt pathway, miR-1 reduces the tumorigenicity of NSCLC cells in a xenograft tumor model ( 48 ). MiR34a was reduced in NSCLC cells, and increased miR34a induced upregulation of PTEN and YY1, inhibition of CDK6 and inactivation of the PI3K/AKT pathway, thereby impeding tumor cell growth ( 49 ). MiR-320a-3p’s expression was markedly downregulated in NSCLC tissues and cells, and cell function studies supported the hypothesis that it functioned as a tumor suppressor gene to prevent cell development by downregulating ELF3 and subsequently deactivating the PI3K/Akt pathway ( 50 ) ( 88 ).…”

Expression level comparison of marker genes related to early embryonic development and tumor growth

“…These nine factors occupy important positions in the large regulatory network of the body (22)(23)(24)(25)(26)(27). Changing of their expression may lead to changes or even loss of control of the regulatory network (22,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). In addition, these factors are highly related to the development and growth, regulatory mechanisms and microenvironment maintenance of early embryos (4,6,17,30,(38)(39)(40)(41)(42).…”