The Association of microRNA-34a With High Incidence and Metastasis of Lung Cancer in Gejiu and Xuanwei Yunnan
Authors: Yue-Yan Zhang
Yan Chen
Da-Lun Li
Chun Hou
Qiu-Chen Cai
Yun-Yi Liu
Ying Zhang
Qian Yao
Qi-Shun Zhu
Hong-Yu Liu
Ya-Kun Yang
Cheng-Wei Gao
Chuan-Hai Cao
Yao Tang
Liu-Xin Zhao
Journal: Frontiers in Oncology (2021)
Discipline: CLINICAL MEDICINE
Keywords: CDK6; PTEN; YY1; growth; lung cancer
Affiliations: School of Life Sciences, Yunnan University, Kunming, China., Yunnan Cancer Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China., Key Laboratory of the University in Yunnan Province for International Cooperation in Intercellular Communications and Regulations, Yunnan University, Kunming, China., School of Chemical Science and Technology, Yunnan University, Kunming, China., Taneja College of Pharmacy, University of South Florida, Tampa, FL, United States.

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. 

Retracted: No

PubPeer comments:
 The manuscript contains several flaws: (1) Fig.2 contains a wound healing assay with several overlapping images: ![file] (2) The upper right FACS plot in Fig.3 A shows an uncompensated FITC channel whereas the other very right FACS plots seem to have compensated FITC channels. ![file] (3) Fig.4 contains at least one spliced WB band, maybe more. Could the authors please provide the original uncrossed images: ![file] , 
 It has been 1.5 years since pointing out these irregularities, could the authors and the journal please take action on this. ,