Lung cancer has a complex etiology that has been attributed to factors such as tobacco use, sex, ethnicity, age, obesity, infection, and genetic contributions that work together to elicit the disease phenotype. The complicated nature of lung cancer may result from the molecular mechanisms underlying cancer progression, as well as a lack of early diagnostic biomarkers and therapeutic targets Yoon et al. 2017)[27]. Numerous studies have shown that lncRNAs play an important role in cancer by regulate the proliferation, migration, invasion, apoptosis, and autophagy of cancer cells (Chen et al. 2017; Schmitt and Chang 2016)[7, 28]. Mechanistically, this regulation occurs through interactions of lncRNA with various cellular molecules and factors, including chromatin, proteins, mRNAs, and microRNAs (Schmitt and Chang 2016; Li et al. 2020; Zhao et al. 2020; Wang et al. 2019)[28–31]. Our results have highlighted the clinical significance of LINC00885 in LUAD and indicate that LINC00885 might be a candidate target for the diagnosis and treatment of LUAD.
Previous reports have shown that LINC00885 plays a key role in cervical cancer. For example, LINC00885 upregulates expression of MACC1 in cervical cancer cells by sponging miR-432-5p, thereby promoting progression of cancer (Chen et al. 2021)[18], indicating that the LINC00885/miR-432-5p/MACC1 axis may serve a potential prognostic biomarker in cervical cancer. Overexpression of LINC00885 has been reported to reverse the inhibitory effects of FOXP3 knockdown on the proliferation and invasion of cervical cancer cells (Liu et al. 2021)[16].
LINC00885 also regulates mTOR, which is involved in cell metabolism, growth, proliferation, and survival (Shawkat et al. 2014)[32]. mTOR enhances protein and lipid synthesis, while reducing autophagy (Laplante and Sabatini 2009; Saxton and Sabatini 2017)[33, 34]. P70S6K is one of the key components of mTOR signal transduction and regulates several proteins involved in protein translation. P70S6K promotes initiation of translation as well as initiation of ribosomal RNA and affects protein expression levels. P70S6K is frequently activated in a wide range of cancers and has a crucial role in several processes that are considered hallmarks of cancer. Therefore, blocking the expression or activity of P70S6K may be a promising strategy for anticancer treatment (Ip et al. 2012)[35].
Hepatocyte growth factor/c-Met signaling plays an important role in promoting angiogenesis, growth, and metastasis of tumors (You and McDonald 2008; Zhang et al. 2018; Matsumoto et al. 2017)[36–38]. Hepatocyte growth factor binds to its receptor, c-Met, which activates several signaling pathways, including the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), PI3K/AKT, NF-κB, and STAT3/5 pathways (Zhang et al. 2018)[37]. There have been several reports indicating that MET is involved in the proliferation, invasion, migration, apoptosis, and other functions of tumor cells (Cai et al. 2020; Liu et al. 2020; Guo et al. 2020)[39–41]. Our results suggest that LINC00885 may be involved in the progression of LUAD by controlling c-Met signaling. Further studies will be required to fully understand the biological mechanisms of LINC00885 in LUAD.
PARP is a key modulator of apoptosis (Farmer et al. 2005)[42]. PARP inhibitors have been approved for the treatment of BRCA-mutant ovarian cancer and breast cancer, and their mechanism is to play a role through the synthetic lethality of DNA repair gene mutations (Slade 2020)[43]. Our data suggest that LINC00885 may inhibit apoptosis via PARP. However, the mechanism needs to be explored in more depth.
Overall, our results show that LINC00885 is involved in the proliferation, invasion, migration, apoptosis, and autophagy of LUAD cells. Future studies are required to further explore the mechanisms via which LINC00885 regulates these cells.