Long non-coding RNA HOTAIR regulates proliferation, migration and invasion of human cervical cancer cells by modulating expression of MAPK1
Authors: Haiying Liu
Jing Liu
Guangzhang Zhao
Journal: Archives of Medical Science (2020)
Discipline: CLINICAL MEDICINE
Keywords: HOTAIR; MAPK1; apoptosis; cell invasion; cell viability
Affiliations: Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China., Communicable Disease Control Division in Qingdao Chengyang District Center for Disease Control and Prevention, Qingdao, Shandong Province, China., Department of Breast Surgery, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China.

Abstract:  Introduction: Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are dysregulated in cancer cells and may be responsible for the development and progression of this disease. Herein, the role and therapeutic potential of aberrantly expressed lncRNA HOTAIR were investigated in cervical cancer. Material and methods: The expression profile of the lncRNA HOTAIR was determined by quantitative RT-PCR. CCK-8 and colony formation assays were used for determination of cell viability. DAPI and annexin V/PI assays were used for detection of apoptosis. Wound healing and transwell assays were used to monitor cell migration and invasion. Results: The results showed that the expression of lncRNA HOTAIR was significantly (p &lt; 0.01) upregulated (up to 4.1-fold) in cervical cancer cell lines. Silencing of lncRNA HOTAIR expression resulted in inhibition of the proliferation of the DoTc2 cervical cancer cells via induction of apoptotic cell death. HOTAIR silencing also resulted in decrease of the migration and the invasive properties of the cervical cancer cells. HOTAIR has been reported to interact with MAPK1 in cancer cells, and in this study MAPK1 was found to be overexpressed (up to 3.7-fold) in all the cervical cancer cells and silencing of HOTAIR inhibited the expression of MAPK1 in DoTc2 cervical cancer cells. Silencing of MAPK1 in DoTc2 cells also inhibited their proliferation and metastasis via induction of apoptosis. Co-transfection experiments showed that silencing of MAPK1 and lncRNA HOTAIR causes inhibition of DoTc2 cell growth synergistically. Conclusions: These results indicate that lncRNA HOTAIR may prove to be an important therapeutic target for management of cervical cancer. 

Retracted: No

PubPeer comments:
 Here are some surprisingly similar blocks of text, all involving the same four citations. It defies belief that the similarity arose by chance. Normal old-fashioned plagiarism is ruled out by the simultaneous submission of many papers. From  Long non-coding RNA HOTAIR regulates proliferation, migration and invasion of human cervical cancer cells by modulating expression of MAPK1 [(Liu, Liu Zhao, 2020)] : * Cervical cancer, being one of the common types of cancers in women, is ranked as the second most prevalent cancer worldwide [1]. Although cervical cancer is more frequent in underdeveloped countries, it still accounts for 10% of all cancers in women [2]. Approximately 0.37 million new cervical cancer cases are detected throughout the globe annually [3]. The treatment for cervical cancer involves radical hysterectomy, chemotherapy and or radiotherapy [4]. However, the clinical outcomes are still unsatisfactory, owing to the adverse effects of chemotherapeutic agents and the dearth of potent therapeutic targets. Hence, the identification of novel, effective and safer anticancer agents and efficient therapeutic targets may help to curb the incidence of cervical cancer and enhance the overall survival rate.  Icariin inhibits the growth of human cervical cancer cells by inducing apoptosis and autophagy by targeting mTOR PI3K AKT signalling pathway [(Huang, Xie Liu 2019)] : * Cervical cancer, being one of the common types of cancers in women, is ranked as second most prevalent cancer world over [11]. Although, cervical cancer is more frequent in underdeveloped countries, it still accounts for 10% of all the cancers in women [12]. Approximately 0.37 million new cervical cancer cases are detected annually worldwide [13]. The treatment for cervical cancer involves surgery, chemotherapy and or radiotherapy [14]. However, the currently available chemotherapeutic agents can create adverse effects, negatively impacting the patient quality of life [15]. Hence, the identification of novel, effective and safer anticancer agents is required to improve the therapeutic results of cervical cancer.*  Scopoletin exerts anticancer effects on human cervical cancer cell lines by triggering apoptosis, cell cycle arrest, inhibition of cell invasion and PI3K AKT signalling pathway [(Tian et al 2019)] : * Cervical cancer, being one of the common types of cancers in women, ranks second in incidence of cancer world over [1]. Although, cervical cancer is more frequent in underdeveloped countries, it still accounts for 10% of all the cancer in women [2,3]. The treatment of cervical cancer involves radical hysterectomy, chemotherapy and or radiotherapy [4]. However, the currently available chemotherapeutic agents have adverse effects that negatively impact the patient quality of life. Hence, the identification of novel, effective and safer anticancer agents is required to curb the spread of cervical cancer.  Alantolactone exhibits selective antitumor effects in HELA human cervical cancer cells by inhibiting cell migration and invasion, G2 M cell cycle arrest, mitochondrial mediated apoptosis and targeting Nf-kB signalling pathway [(Zhang et al 2019)] : * Cervical cancer is the third most commonly diagnosed malignancy in women with approximately 0.5 million women being diagnosed annually, accounting around 9% of all newly diagnosed cancers [1]. Cervical cancer is generally treated with hysterectomy, radiotherapy and chemotherapy, and causes around 0.3 million deaths annually [2]. Although surgery may prove beneficial at early-stage cervical cancer, most of the cases are diagnosed when the disease has already metastasized. Radiotherapy employed for the treatment of advanced cervical cancer causes adverse effects such as skin reactions, pain and lymphodeama to name a few [3] that impair the quality of the patientu2019s life [4]. Owing to all these factors, the development of efficient therapy for cervical cancer is the need of the hour.  Sparteine exerts anticancer effect on human cervical cancer cells via induction of apoptosis, G0 G1 cell cycle arrest and inhibition of VEGFR2 signalling pathway [(Liang Liu 2019)] : * Cervical cancer imposes huge disease burden on all nations across the globe. Approximately, 260,000 cervical cancer mortalities and 530,000 new cases of cervical cancer were reported in 2012 alone [1]. Owning to disproportionate incidence of cervical cancer in low and high-income nations, it is often referred to as the u2018disease of disparityu2019 [2]. Cervical cancer is ranked the fourth major type of cancer in the world [3]. The treatments for cervical cancer involve radical hysterectomy, chemotherapy and or radiotherapy [4]. From  Bismahanine exerts anticancer effects on human cervical cancer cells by inhibition of growth, migration and invasion via suppression of NF-kB signalling pathway [(Yu et al, 2020)] : * Cervical cancer being one of the common types of cancers in women, is ranked as the second most prevalent cancer world over [1]. Although cervical cancer is more frequent in underdeveloped countries, it still accounts for 10% of all the cancers in women [2]. Approximately 0.37 million new cervical cancer cases are detected throughout the globe annually [3]. Despite the development of biomarkers for early detection, the clinical outcomes are still unsatisfactory. The treatment for cervical cancer involves radical hysterectomy, chemotherapy and or radiotherapy [4]. The currently available chemotherapeutic agents have adverse effects impacting the patient quality of life (QoL). Hence, the identification of novel, effective and safer anticancer agents is required to ameliorate the outcome of this disease.  Ovatodiolide exerts anticancer effects on human cervical cancer cells via mitotic catastrophe, apoptosis and inhibition of NF-kB pathway [(Ou et al 2020)] : * Cervical cancer imposes huge disease burden for populations across the globe. Approximately 0.26 million cervical cancer deaths and 0.53 million new cases of cervical cancer were reported in 2012 alone [10]. Owning to disproportionate incidence of cervical cancer in low and high-income countries, it is often referred to as the u2018disease of disparityu2019 [11]. Cervical cancer represents a major type of cancer [12]. The treatment for cervical cancer involves radical hysterectomy, chemotherapy and or radiotherapy [13].  Camelliol C inhibits viability, migration, and invasion of human cervical cancer cells via induction of apoptosis, G2 M cell cycle arrest, and blocking of PI3K AKT signalling pathway [(An Liu 2020)] : * Globally, cervical cancer is responsible for a significant number of human mortalities. Approximately 0.54 million new cervical cancer cases and 0.25 million cervical cancer-related deaths were reported in 2012 [1]. Cervical cancer is also known as the u2018disease of disparityu2019 owing to its inconsistent incidence in high- and low-income countries [2]. As per the estimates, cervical is the fourth most prevalent type of cancer worldwide, and it is believed that its incidence will increase significantly in the next decade [3]. Treatment of cervical cancer generally involves surgery and subsequent chemotherapy [4]. Nonetheless, the currently used chemotherapy has adverse effects and is less efficacious [5]. Therefore, the development of cervical cancer chemotherapy with no or negligible side effects is needed. , 
 Figure 3G.  LncRNA HOTAIR regulates proliferation of cervical cancer cells via MAPK1. ... G u2013 Annexin V PI staining of NC or SiMAPK1 transfected DoTc2 cells .  Color rectangles for comparison with *[left]* Figure 4 from [Meng, Tang Qiu (2019)] .  Determination of the percentage of the apoptotic Saos-2 cell populations as determined by Annexin V PI staining . *[right]* Figure 4A from [Jia et al (2020)] .  Ovatodiolide induces apoptosis in PC-2 cancer cells. A: Flow cytometric examination of apoptosis analysis of PC-2 cancer cells treated with ovatodiolide .  , 
 *[left]* Figure 1E, 3F from [Liu, Liu Zhao (2020)] .  LncRNA HOTAIR regulates proliferation of cervical cancer cells. ... E u2013 DAPI staining of NC or Si-HOTAIR transfected DoTc2 cells ;  LncRNA HOTAIR regulates proliferation of cervical cancer cells via MAPK1. ... F u2013 DAPI staining of NC or Si-MAPK1 transfected DoTc2 cells . *[right]* Figure 4 from [Gao et al (2019)] .  Oleanolic acid induces apoptosis in the HepG2 cells as indicated by DAPI staining. Oleanolic acid triggered apoptosis as evidenced from nuclear fragmentation of the oleanolic acid-treated HepG2 cells.  Two pairs of panels overlap. , 
 Fig 3E.  Colony formation of the NC or Si-MAPK1 transfected DoTc2 cells .  For comparison with *[left]* Figure 2A of [Hou et al (2020)] .  Clonogenic assay for determination of anticolony potential of Cinnamolide in human cervical HeLa cancer cells. Cinnamolide treatment led to a significant and dose-dependent reduction in the number of cancer cell colonies . *[right]* Fig 2A of [Li et al (2020)] .  miR-7 induces apoptosis in TPC-1 cancer cells. A. Colony formation by TPC-1 cells transfected with miRNC and miR-7 mimics . Plus 180-deg-flipped version.  , 
 Figures 2B, 4B.  LncRNA HOTAIR regulates migration and invasion of cervical cancer cells. ... B u2013 Transwell assay showing invasion of DoTc2 cells in NC or Si-HOTAIR transfected DoTc2 cells ;  MAPK1 silencing inhibits migration and invasion of cervical cancer cells....B u2013 Transwell assay showing invasion of DoTc2 cells in NC or SiMAPK1 transfected DoTc2 cells .  These panels appear to be the originals of Figs 7, 8 from [Xiang, Ming Xu (2020)] . Here inverted for clarity.  , 
 #2 Fig 3G again:  An earlier sighting! Fig 3B from  Long non-coding RNA SPRY4-IT1 promotes development of hepatic cellular carcinoma by interacting with ERRu03b1 and predicts poor prognosis ([Yu et al 2017] ):  ,