Long noncoding RNA HOXA-AS2 accelerates cervical cancer by the miR-509-3p/BTN3A1 axis

Abstract

Objectives Cervical cancer is an aggressive malignant tumour and causes high mortality in women. LncRNA HOXA-AS2 is a tumour promoter in many cancers. The current work was designed to elucidate the functions of HOXA-AS2 in cervical cancer and the underlying regulatory mechanism. Methods qRT-PCR was conducted to reveal RNA levels. A FISH assay was conducted for the identification of the subcellular location of HOXA-AS2. MTT, EdU, Transwell and tube formation were used for detection of cell growth, migration and angiogenesis, respectively. In-vivo studies were conducted to reveal the role of HOXA-AS2 on transplanted tumour growth in mice. Key findings The HOXA-AS2 level was found high in tissues and cells of cervical cancer. Silencing of HOXA-AS2 restrained cell proliferation, migration and invasion. Angiogenesis of HUVECs was restrained after silencing HOXA-AS2. Additionally, HOXA-AS2 upregulated the BTN3A1 by interaction with miR-509-3p. BTN3A1 overexpression rescues the inhibitory effect of silenced HOXA-AS2 on cell phenotypes in cervical cancer. Moreover, xenograft tumour growth in mice was suppressed by HOXA-AS2 depletion and was facilitated by BTN3A1 overexpression. Conclusions HOXA-AS2 accelerates cellular progression in cervical cancer by the miR-509-3p/BTN3A1 axis.

HOXA-AS2 may predict the prognosis of solid tumors among Chinese patients: A meta-analysis and bioinformatic analysis

“…A total of 18 articles including 1181 patients were included, and the cancer types included gastric cancer ( 24 ), colorectal cancer (CRC) ( 29 , 40 ), hepatocellular carcinoma(HCC) ( 26 , 27 , 41 ), breast cancer ( 18 ), non-small cell lung cancer (NSCLC) ( 19 , 22 ), prostate cancer ( 31 ), osteosarcoma ( 36 , 37 ), bladder cancer ( 30 ), oral squamous cell carcinoma (OSCC) ( 13 ), papillary thyroid cancer (PTC) ( 15 , 16 ), cervical cancer ( 35 ) and glioma ( 47 ). The publication years were from 2015 to 2021, and all patients were from China.…”

“…HOXA-AS2 was found to be highly expressed in promyelocytic leukemia for the first time ( 55 ) and has been confirmed to be dysregulated in diverse tumor cells, such as osteosarcoma ( 37 ), glioma ( 56 ), NSCLC ( 20 ), CRC ( 57 ), and cervical cancer ( 35 ). It has also been proven to be involved in the biological behavior of many tumor cells as a high-risk factor.…”

“…In osteosarcoma and cervical cancer, cell function tests show that HOXA-AS2 upregulation promotes tumor cell metastasis, prevents the cell cycle, and epithelial-mesenchymal transition and inhibits apoptosis. Silencing HOXA-AS2 can inhibit the above biological processes ( 35 , 37 ). In hepatocellular carcinoma, HOXA-AS2 expression was significantly increased in both cell lines and HCC tissues and was associated with poor survival and prognosis ( 41 ).…”

“…HOXA-AS2 is a 1048-bp long noncoding RNA located on human chromosome 7p15.2 between the HOXA3 and HOXA4 genes in the HOXA cluster ( 11 ). In recent years, an increasing number of publications have shown that HOXA-AS2 is highly expressed in diverse malignancies, including oral squamous cell carcinoma ( 12 , 13 ), nasopharyngeal carcinoma ( 14 ), thyroid cancer ( 15 , 16 ), breast cancer ( 17 , 18 ), lung cancer ( 19 – 22 ), gallbladder carcinoma ( 23 ), gastric cancer ( 24 , 25 ), hepatocellular carcinoma ( 26 , 27 ), pancreatic cancer ( 28 ), colorectal cancer ( 29 ), bladder cancer ( 30 ), prostate cancer ( 31 ), ovarian cancer ( 32 ), endometrial cancer ( 33 ), cervical cancer ( 34 , 35 ), osteosarcoma ( 36 , 37 ) and glioblastoma ( 38 ). Cell function tests showed that high HOXA-AS2 expression can promote the proliferation and invasion of cancer cells, inhibit apoptosis, and affect the cancer cell cycle ( 21 , 32 ).…”

HOXA-AS2 may be a potential prognostic biomarker in human cancers: A meta-analysis and bioinformatics analysis

“…Previous studies found that HOXA-AS2 was up-regulated in certain cancers. The increased expression of HOXA-AS2 typically predicts poor prognosis for patients with several cancers including cervical cancer (CC) ( Chen and He, 2021 ), oral squamous cell carcinoma (OSCC) ( Chen et al, 2021 ), lung cancer (LC) ( Li and Jiang, 2017 ; Cui et al, 2019 ; Liu et al, 2019 ), colorectal cancer (CRC) ( Li et al, 2016 ; Ding et al, 2017 ), breast cancer (BC) ( Fang et al, 2017 ), thyroid cancer (TC) ( Xia et al, 2018 ; Jiang et al, 2019 ), hepatocellular carcinoma (HCC) ( Wang et al, 2016 ; Zhang et al, 2018 ; Lu et al, 2020 ), acute myeloid leukemia (AML) ( Qu et al, 2020 ), bladder cancer ( Wang F. et al, 2019 ), osteosarcoma (OSA) ( Wang et al, 2018 ; Wang L. et al, 2019 ), lower-grade glioma (LGG) ( Wu et al, 2019 ), prostate cancer (PCa) ( Xiao and Song, 2020 ), gastric cancer (GC) ( Xie et al, 2015 ). A high level of HOXA-AS2 expression is associated with poor overall survival (OS) and clinicopathological characteristics such as differentiation, tumor node metastasis (TNM) stage, lymph node metastasis (LNM).…”