tRNA‐derived RNA fragments (tRFs), non‐coding single‐stranded RNAs with 14–35 nt in length, were found to play important roles in gene regulation, even in carcinogenesis. In this study, we investigated the expression of tRF‐Leu‐CAG in human non‐small cell lung cancer (NSCLC) and its function in the cell proliferation and cell cycle of NSCLC. The expression level of tRF‐Leu‐CAG was detected in NSCLC tissues, cell lines, and sera. tRF‐Leu‐CAG RNA levels were higher in NSCLC tumor tissues than in normal tissues, and also upregulated in NSCLC cell lines. A significant relationship was observed between stage progression and tRF‐Leu‐CAG in NSCLC sera. We found that in H1299 cells, inhibition of tRF‐Leu‐CAG suppressed cell proliferation and impeded cell cycle. AURKA was also repressed with the knockdown of tRF‐Leu‐CAG. Thus, our study revealed that tRF‐Leu‐CAG may be involved in regulating AURKA and could be a new diagnostic marker and potential therapeutic target in NSCLC.

MicroRNAs (miRNAs) comprise a class of short, non-coding RNAs that directly target 3′UTR of mRNA, causing subsequent degradation or suppression of translation. Here, we verified that miR-199a-5p was significantly down-regulated in mouse NSCLC tissues and human patient samples. To further study the function of miR-199a-5p, lentivirus system was adopted to construct stably over-expressing miR-199a-5p A549, SPC-A1 and H1299 cell lines. Then, miR-199a-5p played a tumor suppression role via directly targeting MAP3K11 gene in non-small cell lung cancer (NSCLC). Elevated miR-199a-5p suppressed cell proliferation and arrested cell cycle in G1 phase. We found that MAP3K11 was negatively correlated with miR-199a-5p in NSCLC patient tissues and mouse xenograft tumors. Our results suggest that miR-199a-5p together with its target gene MAP3K11 is a key factor and constitutes a complicated regulation network in NSCLC.

MicroRNAs are a class of non-coding single-stranded RNA, 20-23 nucleotide in length, which can be involved in the regulation of gene expression. Through binding with 3'-untranslated regions (3'-UTR), microRNAs can cause degradation of target mRNAs or inhibition of translation, and thus regulating the expression of genes at the post-transcriptional level. In this study, we found that miR-486-5p was significantly downregulated in non-small cell lung cancer (NSCLC) tissues and cell lines, suggesting that miR-486-5p might function as a tumor suppressor in lung cancer. Additionally, we showed that CDK4, an oncogene that plays an important role in cell cycle G1/S phase progression, was directly targeted by miR-486-5p. Furthermore, our data reveals that knockdown of CDK4 by siRNA can inhibit cell proliferation, promote apoptosis, and impede cell-cycle progression. In epigenetics, the upstream promoter of miR-486-5p was strongly regulated by methylation in NSCLC. Collectively, our results suggest that miR-486-5p could not only inhibit NSCLC by downregulating the expression of CDK4, but also be as a promising and potent therapy in the near future.

Chemoresistance is one of the major reasons leading to ovarian cancer high mortality and poor survival. Studies have shown that the alteration of cellular autophagy is associated with cancer cell chemoresistance. Here, we investigated whether the ovarian cancer chemoresistance is associated with the autophagy induced by the inhibitor of DNA binding 1 (ID1). By using gene overexpression or silencing, luciferase assay and human specimens, we show that ID1 induces high autophagy and confers cancer cell chemoresistance. The mechanistic study demonstrates that ID1 first activates the NF-κB signaling through facilitating the nuclear translocation of NF-κB p65, which strengthens the expression and secretion of IL-6 from cancer cells to subsequently activate the signal transducer and activator of transcription 3 (STAT3) through the protein phosphorylation at Y705. We further identified that STAT3 functions to promote the transcription of the activating transcription factor 6 (ATF6), which induces endoplasmic reticulum stress to promote cellular autophagy, granting cancer cell resistance to both cisplatin and paclitaxel treatment. Moreover, we found a significant correlation between the expression of ID1 and ATF6 in 1104 high grade serous ovarian cancer tissues, and that patients with the high expression of ID1 or ATF6 were resistant to platinum treatment and had the poor overall survival and progression-free survival. Thus, we have uncovered a mechanism in which ID1 confers cancer cell chemoresistance largely through the STAT3/ATF6-induced autophagy. The involved molecules, including ID1, STAT3, and ATF6, may have a potential to be targeted in combination with chemotherapeutic agents to improve ovarian cancer survival.

MicroRNAs (miRNAs) are dysregulated in cancers, including human non-small cell lung cancer (NSCLC). The function of MicroRNA-107-5p (miR-107-5p) in NSCLC is not fully elucidated. Epidermal growth factor receptor (EGFR) is a cancer-driven gene in tumorigenesis. In this study, we found that miR-107-5p was significantly decreased in NSCLC tissues and NSCLC cell lines. Moreover, our results indicated that miR-107-5p could suppress cell proliferation, inhibit metastasis, impede cell cycle, and promote apoptosis via directly targeting EGFR. We also investigated roles of miR-107-5p in vivo. The results showed that it could inhibit tumor growth. Therefore, our study demonstrated that miR-107-5p not only suppressed the progression in NSCLC cells by inhibiting the expression of EGFR, but also could be a promising and a new potential therapeutic target for lung cancer.

Nuclear factor κB (NF-κB) acts as a nuclear factor that is composed of five main subunits. It is a pluripotent and crucial dimer transcription factor that has a close relationship with many serious illnesses, especially its influences on cell proliferation, inflammation, and cancer initiation and progression. NF-κB acts as part of the signaling pathway and determines its effect on the expression of several other genes, such as epidermal growth factor receptor (EGFR), p53, signal transducer and activator of transcription 3 (STAT3), and non-coding RNA (ncRNA). Continuous activation of the NF-κB signaling pathway has been seen in many cancer types. While the NF-κB signaling pathway is tightly regulated in physiological settings, quite frequently it is constitutively activated in cancer, and the molecular biology mechanism underlying the deregulated activation of NF-κB signaling remains unclear. In this review, we discuss the regulatory role and possible clinical significance of ncRNA (microRNA [miRNA] and long non-coding RNA [lncRNA]) in NF-κB signaling in cancer, including in the conversion of inflammation to carcinogenesis. Non-coding RNA plays an essential and complex role in the NF-κB signaling pathway. NF-κB activation can also induce the ncRNA status. Targeting NF-κB signaling by ncRNA is becoming a promising strategy of drug development and cancer treatment.

Accounting for more than 70% of ovarian cancer cases, epithelial ovarian malignancy has a low 5-year survival rate. MicroRNAs may be targeted in the clinical treatment of the disease. In this study, we first found that miR-1251-5p was significantly upregulated in human ovarian cancer cell lines and tissues with the cancer progression and stages. Overexpression or inhibition of miR-1251-5p promoted or impeded cell proliferation and cell cycle progression. Subsequently, TBCC, one of the tubulin-binding cofactors (TBCs), was identified as a target of miR-1251-5p to be negatively associated with cell cycle and autophagy. Exogenous overexpression of TBCC inhibited the expressions of CDK4 and LC3BII, but it promoted the expressions of a/b-tubulin and p62 to suppress cell growth and autophagy, particularly under the starving condition; whereas the introduction of miR-1251-5p in TBCC-overexpressing cells rescued the suppressive effects of TBCC on cell cycle and autophagy through the inverse regulation of the above proteins. Finally, miR-1251-5p was proven to enhance xenograft tumor growth through the downregulation of TBCC but upregulation of Ki67 and LC3B in xenograft tumor tissues. Collectively, these results suggest that miR-1251-5p functions as an oncogene to suppress TBCC and a/b-tubulin expression. Thus, the miR-1251-5p/TBCC/a/b-tubulin axis may be targeted for ovarian cancer treatment.

tRNA-derived small RNAs (tRFs), a kind of noncoding RNAs, are generated from transfer RNAs. tRFs have some types according to their source and sizes.They play important roles in cell life and carcinogenesis. In this paper, we review the biogenesis and biological properties. We also focus on current progress of tRFs and some tsRNAs such as tRF-Leu-CAG, which have been studied or will be further investigated in tumorgenesis and diagnostic biomarkers in the clinic.