Long non-coding RNA DILC suppresses bladder cancer cells progression.

Accumulative researches have demonstrated the critical functions of long non-coding RNAs (lncRNAs) in the progression of malignant tumors, including bladder cancer (BC). Our previous studies showed that lnc-DILC was an important tumor suppressor gene in both liver cancer and colorectal cancer. However, the role of lnc-DILC in BC remains to be elucidated. In the present study, we for first found that lnc-DILC was downregulated in human bladder cancer tissues. Lnc-DILC overexpression suppressed the proliferation, metastasis and expansion of bladder cancer stem cells (CSCs). Mechanically, lnc-DILC suppressed BC cells progression via STAT3 pathway. Special STAT3 inhibitor S3I-201 diminished the discrepancy of growth, metastasis and self-renewal ability between lnc-DILC-overexpression BC cells and their control cells, which further confirmed that STAT3 was acquired for lnc-DILC-disrupted BC cell growth, metastasis and self-renewal. Taken together, our results suggest that lnc-DILC is a novel bladder tumor suppressor and indicate that lnc-DILC inhibits BC progression via inactivating STAT3 signaling.

Long non-coding RNA DILC promotes the progression of gallbladder carcinoma.

Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) contribute to tumorigenesis, progression and recurrence of various malignancies including Gallbladder carcinoma (GBC). Lnc-DILC is reported to be the tumor suppressor gene to play an important role in liver cancer stem cells (CSCs). However, the role of lnc-DILC in GBC remains to be elucidated. Herein, we show that lnc-DILC is upregulated in gallbladder CSCs and GBC patients' tissues. Knockdown of lnc-DILC attenuates the self-renewal, tumorigenicity, proliferation and metastasis of gallbladder CSCs. Mechanistically, lnc-DILC promotes gallbladder CSCs expansion via Wnt/ß-catenin pathway. Special Wnt/ß-catenin inhibitor FH535 diminishes the discrepancy of self-renewal, growth and metastasis between lnc-DILC interference GBC cells and their control cells. In conclusion, lnc-DILC drives gallbladder CSCs self-renewal, tumorigenicity, proliferation and metastasis by activating Wnt/ß-catenin signaling, and may therefore prove to be a potential therapeutic target for GBC patients.

Long non-coding RNA DILC suppresses cell proliferation and metastasis in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors and one of the leading causes of cancer-related death in both men and women. The prognosis of CRC remains poor due to the advanced stage and cancer metastasis at the time of diagnosis. However, the exact mechanism of tumorigenesis in CRC remains unclear. Long non-coding RNAs (lncRNAs), which refer to transcripts longer than 200 nucleotides that are not translated into protein, are known to play important roles in multiple human cancers. Lnc-DILC is reported to be an important tumor suppressor gene and its inactivation is closely associated with liver cancer stem cells. However, the role of lnc-DILC in CRC remains to be elucidated. In the present study, we observed that lnc-DILC overexpression inhibited the growth and metastasis of CRC cells. Consistently, lnc-DILC knockdown facilitated the proliferation and metastasis of CRC cells. Mechanically, lnc-DILC suppressed CRC cell progression via IL-6/STAT3 signaling inactivation. More importantly, the specific STAT3 inhibitor S3I-201 and IL-6R inhibitor tocilizumab abolished the discrepancy of growth and metastasis capacity between lnc-DILC-interference CRC cells and control cells, which further confirmed that IL-6/STAT3 signaling was required in lnc-DILC-disrupted CRC cell growth and metastasis. Taken together, our results suggest that lnc-DILC is a novel CRC suppressor and may prove to be an inhibitor of CRC progression by inactivating IL-6/STAT3 signaling.

Isofraxidin inhibited proliferation and induced apoptosis via blockage of Akt pathway in human colorectal cancer cells.

BACKGROUND: Isofraxidin (IF), a natural coumarin compound, has been reported to possess anti-cancer activity in human liver cancer. However, whether IF is involved in the regulation of colorectal cancer tumorigenesis and development has been not well elucidated. METHODS: The cell proliferation were assessed by Cell Counting Kit-8 (CCK-8) and colony formation test, respectively. The transwell assays were conducted to estimate cell migration and invasion abilities. Further, cell apoptosis was evaluated by confocal microscopy analysis, flow cytometry detection and TdT-mediated dUTP Nick-End Labeling (TUNEL) method. Western blot were performed to detect the expression of related protein. RESULTS: Herein, the result indicated that IF remarkably bated cell proliferation in human colorectal cancer cells HT-29 and SW-480 in a dose- and time-dependent manner. In addition, IF treatment showed obvious inhibitory activity to cell colony formation in HT-29 and SW-480 cells. Confocal microscopy analysis and flow cytometry detection revealed that IF dramatically induced cell apoptosis in HT-29 and SW-480 cells compared with the control. And IF markedly decreased the expression of anti-apoptotic protein bcl-2, whereas the expression of pro-apoptotic proteins, including caspase-3, caspase-9 and bax, notably increased in HT-29 and SW-480 cells. Besides, IF blocked Akt pathway via inhibition expression of p-Akt. Furthermore, MK2206, an Akt inhibitor, could inhibit cell colony formation and induced apoptosis. This effect is even more obvious in the presence of MK2206 and IF compared to that of either agent alone. CONCLUSIONS: Together, the present study reports a novel use of IF in mitigating human colorectal cancer proliferation and inducing apoptosis via blockage of Akt pathway.